U.S. patent application number 12/621903 was filed with the patent office on 2010-06-24 for fungicidal triphenyl-substituted pyridones.
This patent application is currently assigned to E.I. DU PONT DE NEMOURS AND COMPANY. Invention is credited to Bruce Lawrence Finkelstein.
Application Number | 20100160385 12/621903 |
Document ID | / |
Family ID | 42267033 |
Filed Date | 2010-06-24 |
United States Patent
Application |
20100160385 |
Kind Code |
A1 |
Finkelstein; Bruce
Lawrence |
June 24, 2010 |
FUNGICIDAL TRIPHENYL-SUBSTITUTED PYRIDONES
Abstract
Disclosed are compounds of Formula 1, including all geometric
and stereoisomers, N-oxides, and salts thereof, ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and n are as defined in
the disclosure. Also disclosed are compositions containing the
compounds of Formula 1 and methods for controlling plant disease
caused by a fungal pathogen comprising applying an effective amount
of a compound or a composition of the invention.
Inventors: |
Finkelstein; Bruce Lawrence;
(Newark, DE) |
Correspondence
Address: |
E I DU PONT DE NEMOURS AND COMPANY;LEGAL PATENT RECORDS CENTER
BARLEY MILL PLAZA 25/1122B, 4417 LANCASTER PIKE
WILMINGTON
DE
19805
US
|
Assignee: |
E.I. DU PONT DE NEMOURS AND
COMPANY
Wilmington
DE
|
Family ID: |
42267033 |
Appl. No.: |
12/621903 |
Filed: |
November 19, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61139027 |
Dec 19, 2008 |
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Current U.S.
Class: |
514/345 ;
546/290 |
Current CPC
Class: |
C07D 213/68 20130101;
A01N 43/40 20130101 |
Class at
Publication: |
514/345 ;
546/290 |
International
Class: |
A01N 43/40 20060101
A01N043/40; C07D 213/63 20060101 C07D213/63; A01P 3/00 20060101
A01P003/00 |
Claims
1. A compound selected from Formula 1, N-oxides, and salts thereof,
##STR00014## wherein each R.sup.1 is independently halogen, cyano,
hydroxy, amino, nitro, --CHO, C.sub.1-C.sub.6 alkyl,
C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6
haloalkyl, C.sub.2-C.sub.6 haloalkenyl, C.sub.2-C.sub.6
haloalkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6
halocycloalkyl, C.sub.4-C.sub.8 alkylcycloalkyl, C.sub.4-C.sub.8
cycloalkylalkyl, C.sub.5-C.sub.8 alkylcycloalkylalkyl,
C.sub.3-C.sub.6 cycloalkenyl, C.sub.2-C.sub.6 alkoxyalkyl,
C.sub.2-C.sub.6 alkylthioalkyl, C.sub.2-C.sub.6 alkylsulfinylalkyl,
C.sub.2-C.sub.6 alkylsulfonylalkyl, C.sub.2-C.sub.6
alkylaminoalkyl, C.sub.3-C.sub.6 dialkylaminoalkyl, C.sub.2-C.sub.6
alkylcarbonyl, C.sub.2-C.sub.6 haloalkylcarbonyl, C.sub.2-C.sub.6
alkoxycarbonyl, C.sub.2-C.sub.6 alkylaminocarbonyl, C.sub.3-C.sub.8
dialkylaminocarbonyl, C.sub.2-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6
hydroxyalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy,
C.sub.3-C.sub.6 cycloalkoxy, C.sub.3-C.sub.6 halocycloalkoxy,
C.sub.2-C.sub.6 alkoxyalkoxy, C.sub.3-C.sub.6 alkoxycarbonylalkyl,
C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 haloalkylthio,
C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 haloalkylsulfinyl,
C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 haloalkylsulfonyl,
C.sub.3-C.sub.9 trialkylsilyl, C.sub.1-C.sub.6 alkylamino,
C.sub.2-C.sub.6 dialkylamino, C.sub.2-C.sub.6 haloalkylamino,
C.sub.2-C.sub.6 halodialkylamino, C.sub.2-C.sub.6
alkylcarbonylamino, C.sub.2-C.sub.6 haloalkylcarbonylamino,
C.sub.1-C.sub.6 alkylsulfonylamino or C.sub.1-C.sub.6
haloalkylsulfonylamino; R.sup.2 is F or Cl; R.sup.3 is halogen or
methoxy; R.sup.4 is H or halogen; and n is an integer selected from
0, 1, 2, 3, 4 and 5.
2. A compound of claim 1 wherein: each R.sup.1 is independently
halogen, cyano, nitro, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6
alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6 haloalkyl,
C.sub.2-C.sub.6 alkoxyalkyl, C.sub.2-C.sub.6 alkylcarbonyl,
C.sub.2-C.sub.6 alkoxycarbonyl, C.sub.2-C.sub.6 alkylaminocarbonyl,
C.sub.3-C.sub.8 dialkylaminocarbonyl, C.sub.2-C.sub.6 cyanoalkyl,
C.sub.1-C.sub.6 hydroxyalkyl, C.sub.1-C.sub.6 alkoxy,
C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 alkylsulfinyl,
C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 alkylamino,
C.sub.2-C.sub.6 dialkylamino or C.sub.2-C.sub.6
alkylcarbonylamino.
3. A compound of claim 2 wherein: each R.sup.1 is independently is
halogen, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl,
C.sub.1-C.sub.6 haloalkyl, C.sub.2-C.sub.6 alkylcarbonyl,
C.sub.2-C.sub.6 alkoxycarbonyl or C.sub.1-C.sub.6 alkoxy; R.sup.3
is Cl, F, Br or methoxy; and R.sup.4 is H, Cl, F or Br.
4. A compound of claim 3 wherein: each R.sup.1 is independently
halogen, C.sub.1-C.sub.6 alkyl or C.sub.1-C.sub.6 alkoxy; R.sup.3
is F or methoxy; and R.sup.4 is Cl or F.
5. A compound of claim 4 wherein: R.sup.2 is F. R.sup.3 is F or
methoxy; R.sup.4 is Cl or F; and n is 0 or 1.
6. A compound of claim 5 wherein: R.sup.3 is attached at the para
position.
7. A compound of claim 6 wherein: R.sup.3 is F.
8. A compound of claim 6 wherein: R.sup.3 is methoxy.
9. A fungicidal composition comprising (a) a compound of claim 1;
and (b) at least one other fungicide.
10. A fungicidal composition comprising (a) a compound of claim 1;
and (b) at least one additional component selected from the group
consisting of surfactants, solid diluents and liquid diluents.
11. A method for controlling plant diseases caused by fungal plant
pathogens comprising applying to the plant or portion thereof, or
to the plant seed, a fungicidally effective amount of a compound of
claim 1.
Description
FIELD OF THE INVENTION
[0001] This invention relates to certain substituted pyridones,
their N-oxides, salts and compositions, and methods of their use as
fungicides.
BACKGROUND OF THE INVENTION
[0002] The control of plant diseases caused by fungal plant
pathogens is extremely important in achieving high crop efficiency.
Plant disease damage to ornamental, vegetable, field, cereal, and
fruit crops can cause significant reduction in productivity and
thereby result in increased costs to the consumer. Many products
are commercially available for these purposes, but the need
continues for new compounds which are more effective, less costly,
less toxic, environmentally safer or have different sites of
action.
[0003] U.S. Pat. No. 4,757,081 discloses certain
1,2,6-triphenyl-4(1H)-pyridinone derivatives of Formula i
##STR00002##
and their use as fungicides.
[0004] European Patent 304057 discloses pyridinone derivatives of
Formula ii
##STR00003##
and their use as fungicides.
SUMMARY OF THE INVENTION
[0005] This invention is directed to compounds of Formula 1
(including all geometric and stereoisomers), N-oxides, and salts
thereof, agricultural compositions containing them and their use as
fungicides:
##STR00004##
wherein [0006] each R.sup.1 is independently halogen, cyano,
hydroxy, amino, nitro, --CHO, C.sub.1-C.sub.6 alkyl,
C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6
haloalkyl, C.sub.2-C.sub.6 haloalkenyl, C.sub.2-C.sub.6
haloalkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6
halocycloalkyl, C.sub.4-C.sub.8 alkylcycloalkyl, C.sub.4-C.sub.8
cycloalkylalkyl, C.sub.5-C.sub.8 alkylcycloalkylalkyl,
C.sub.3-C.sub.6 cycloalkenyl, C.sub.2-C.sub.6 alkoxyalkyl,
C.sub.2-C.sub.6 alkylthioalkyl, C.sub.2-C.sub.6 alkylsulfinylalkyl,
C.sub.2-C.sub.6 alkylsulfonylalkyl, C.sub.2-C.sub.6
alkylaminoalkyl, C.sub.3-C.sub.6 dialkylaminoalkyl, C.sub.2-C.sub.6
alkylcarbonyl, C.sub.2-C.sub.6 haloalkylcarbonyl, C.sub.2-C.sub.6
alkoxycarbonyl, C.sub.2-C.sub.6 alkylaminocarbonyl, C.sub.3-C.sub.8
dialkylaminocarbonyl, C.sub.2-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6
hydroxyalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy,
C.sub.3-C.sub.6 cycloalkoxy, C.sub.3-C.sub.6 halocycloalkoxy,
C.sub.2-C.sub.6 alkoxyalkoxy, C.sub.3-C.sub.6 alkoxycarbonylalkyl,
C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 haloalkylthio,
C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 haloalkylsulfinyl,
C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 haloalkylsulfonyl,
C.sub.3-C.sub.9 trialkylsilyl, C.sub.1-C.sub.6 alkylamino,
C.sub.2-C.sub.6 dialkylamino, C.sub.2-C.sub.6 haloalkylamino,
C.sub.2-C.sub.6 halodialkylamino, C.sub.2-C.sub.6
alkylcarbonylamino, C.sub.2-C.sub.6 haloalkylcarbonylamino,
C.sub.1-C.sub.6 alkylsulfonylamino or C.sub.1-C.sub.6
haloalkylsulfonylamino; [0007] R.sup.2 is F or Cl; [0008] R.sup.3
is halogen or methoxy; [0009] R.sup.4 is H or halogen; and [0010] n
is an integer selected from 0, 1, 2, 3, 4 and 5.
[0011] More particularly, this invention pertains to a compound of
Formula 1 (including all geometric and stereoisomers), an N-oxide,
or a salt thereof.
[0012] This invention also relates to a fungicidal composition
comprising a compound of Formula 1 and at least one additional
component selected from the group consisting of surfactants, solid
diluents and liquid diluents.
[0013] This invention also relates to a fungicidal composition
comprising a mixture of a compound of Formula 1 and at least one
other fungicide (e.g., at least one other fungicide having a
different site of action).
[0014] This invention further relates to a method for controlling
plant diseases caused by fungal plant pathogens comprising applying
to the plant or portion thereof, or to the plant seed, a
fungicidally effective amount of a compound of the invention (e.g.,
as a composition described herein).
DETAILS OF THE INVENTION
[0015] As used herein, the terms "comprises," "comprising,"
"includes," "including," "has," "having", "contains" or
"containing" or any other variation thereof, are intended to cover
a non-exclusive inclusion. For example, a composition, process,
method, article, or apparatus that comprises a list of elements is
not necessarily limited to only those elements but may include
other elements not expressly listed or inherent to such
composition, process, method, article, or apparatus. Further,
unless expressly stated to the contrary, "or" refers to an
inclusive or and not to an exclusive or. For example, a condition A
or B is satisfied by any one of the following: A is true (or
present) and B is false (or not present), A is false (or not
present) and B is true (or present), and both A and B are true (or
present).
[0016] Also, the indefinite articles "a" and "an" preceding an
element or component of the invention are intended to be
nonrestrictive regarding the number of instances (i.e. occurrences)
of the element or component. Therefore "a" or "an" should be read
to include one or at least one, and the singular word form of the
element or component also includes the plural unless the number is
obviously meant to be singular.
[0017] As referred to in the present disclosure and claims, "plant"
includes members of Kingdom Plantae, particularly seed plants
(Spermatopsida), at all life stages, including young plants (e.g.,
germinating seeds developing into seedlings) and mature,
reproductive stages (e.g., plants producing flowers and seeds).
Portions of plants include geotropic members typically growing
beneath the surface of the growing medium (e.g., soil), such as
roots, tubers, bulbs and corms, and also members growing above the
growing medium, such as foliage (including stems and leaves),
flowers, fruits and seeds.
[0018] As referred to herein, the term "seedling", used either
alone or in a combination of words means a young plant developing
from the embryo of a seed.
[0019] In the above recitations, the term "alkyl", used either
alone or in compound words such as "alkylthio" or "haloalkyl"
includes straight-chain or branched alkyl, such as, methyl, ethyl,
n-propyl, i-propyl, or the different butyl, pentyl or hexyl
isomers. "Alkenyl" includes straight-chain or branched alkenes such
as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl,
pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such
as 1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes
straight-chain or branched alkynes such as ethynyl, 1-propynyl,
2-propynyl and the different butynyl, pentynyl and hexynyl isomers.
"Alkynyl" can also include moieties comprised of multiple triple
bonds such as 2,5-hexadiynyl.
[0020] "Alkoxy" includes, for example, methoxy, ethoxy,
n-propyloxy, isopropyloxy and the different butoxy, pentoxy and
hexyloxy isomers. "Alkylthio" includes branched or straight-chain
alkylthio moieties such as methylthio, ethylthio, and the different
propylthio, butylthio, pentylthio and hexylthio isomers.
"Alkylsulfinyl" includes both enantiomers of an alkylsulfinyl
group. Examples of "alkylsulfinyl" include CH.sub.3S(.dbd.O),
CH.sub.3CH.sub.2S(.dbd.O), CH.sub.3CH.sub.2CH.sub.2S(.dbd.O),
(CH.sub.3).sub.2CHS(.dbd.O) and the different butylsulfinyl,
pentylsulfinyl and hexylsulfinyl isomers. Examples of
"alkylsulfonyl" include CH.sub.3S(.dbd.O).sub.2,
CH.sub.3CH.sub.2S(.dbd.O).sub.2,
CH.sub.3CH.sub.2CH.sub.2S(.dbd.O).sub.2,
(CH.sub.3).sub.2CHS(.dbd.O).sub.2, and the different butylsulfonyl,
pentylsulfonyl and hexylsulfonyl isomers. "Alkylamino" includes an
NH radical substituted with straight-chain or branched alkyl.
Examples of "alkylamino" include CH.sub.3CH.sub.2NH,
CH.sub.3CH.sub.2CH.sub.2NH, and (CH.sub.3).sub.2CHCH.sub.2NH.
Examples of "dialkylamino" include (CH.sub.3).sub.2N,
(CH.sub.3CH.sub.2CH.sub.2).sub.2N and
CH.sub.3CH.sub.2(CH.sub.3)N.
[0021] "Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples
of "alkoxyalkyl" include CH.sub.3OCH.sub.2,
CH.sub.3OCH.sub.2CH.sub.2, CH.sub.3CH.sub.2OCH.sub.2,
CH.sub.3CH.sub.2CH.sub.2CH.sub.2OCH.sub.2 and
CH.sub.3CH.sub.2OCH.sub.2CH.sub.2. "Alkoxyalkoxy" denotes alkoxy
substitution on alkoxy.
[0022] "Alkylthioalkyl" denotes alkylthio substitution on alkyl.
Examples of "alkylthioalkyl" include CH.sub.3SCH.sub.2,
CH.sub.3SCH.sub.2CH.sub.2, CH.sub.3CH.sub.2SCH.sub.2,
CH.sub.3CH.sub.2CH.sub.2CH.sub.2SCH.sub.2 and
CH.sub.3CH.sub.2SCH.sub.2CH.sub.2; "alkylsulfinylalkyl" and
"alkylsulfonylalkyl" include the corresponding sulfoxides and
sulfones, respectively. "Alkylaminoalkyl" denotes alkylamino
substitution on alkyl. Examples of "alkylaminoalkyl" include
CH.sub.3NHCH.sub.2, CH.sub.3NHCH.sub.2CH.sub.2,
CH.sub.3CH.sub.2NHCH.sub.2,
CH.sub.3CH.sub.2CH.sub.2CH.sub.2NHCH.sub.2 and
CH.sub.3CH.sub.2NHCH.sub.2CH.sub.2. Examples of "dialkylaminoalkyl"
include ((CH.sub.3).sub.2CH).sub.2NCH.sub.2,
(CH.sub.3CH.sub.2CH.sub.2).sub.2NCH.sub.2 and
CH.sub.3CH.sub.2(CH.sub.3)NCH.sub.2CH.sub.2.
[0023] "Cyanoalkyl" denotes an alkyl group substituted with one
cyano group. Examples of "cyanoalkyl" include NCCH.sub.2,
NCCH.sub.2CH.sub.2 and CH.sub.3CH(CN)CH.sub.2.
[0024] "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl,
cyclopentyl and cyclohexyl. The term "alkylcycloalkyl" denotes
alkyl substitution on a cycloalkyl moiety and includes, for
example, ethylcyclopropyl, i-propylcyclobutyl, 3-methylcyclopentyl
and 4-methylcyclohexyl. The term "cycloalkylalkyl" denotes
cycloalkyl substitution on an alkyl moiety. Examples of
"cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and
other cycloalkyl moieties bonded to straight-chain or branched
alkyl groups. The term "cycloalkoxy" denotes cycloalkyl linked
through an oxygen atom such as cyclopentyloxy and cyclohexyloxy.
"Alkylcycloalkylalkyl" denotes an alkyl group substituted with
alkylcycloalkyl. Examples of "alkylcycloalkylalkyl" include 1-, 2-,
3- or 4-methyl or -ethyl cyclohexylmethyl. "Cycloalkenyl" includes
groups such as cyclopentenyl and cyclohexenyl as well as groups
with more than one double bond such as 1,3- and
1,4-cyclohexadienyl.
[0025] "Alkylcarbonyl" denotes a straight-chain or branched alkyl
moieties bonded to a C(.dbd.O) moiety. Examples of "alkylcarbonyl"
include CH.sub.3C(.dbd.O), CH.sub.3CH.sub.2CH.sub.2C(.dbd.O) and
(CH.sub.3).sub.2CHC(.dbd.O). Examples of "alkoxycarbonyl" include
CH.sub.3OC(.dbd.O), CH.sub.3CH.sub.2OC(.dbd.O),
CH.sub.3CH.sub.2CH.sub.2C(.dbd.O), (CH.sub.3).sub.2CHOC(.dbd.O) and
the different butoxy- or pentoxycarbonyl isomers. Examples of
"alkylaminocarbonyl" include CH.sub.3NHC(.dbd.O),
CH.sub.3CH.sub.2NHC(.dbd.O), CH.sub.3CH.sub.2CH.sub.2NHC(.dbd.O),
(CH.sub.3).sub.2CHNHC(.dbd.O) and the different butylamino- or
pentylaminocarbonyl isomers. Examples of "dialkylaminocarbonyl"
include (CH.sub.3).sub.2NC(.dbd.O),
(CH.sub.3CH.sub.2).sub.2NC(.dbd.O),
CH.sub.3CH.sub.2(CH.sub.3)NC(.dbd.O),
(CH.sub.3).sub.2CH(CH.sub.3)NC(.dbd.O) and
CH.sub.3CH.sub.2CH.sub.2(CH.sub.3)NC(.dbd.O). "Alkoxycarbonylalkyl"
denotes alkoxycarbonyl substitution on straight-chain or branched
alkyl. Examples of "alkoxycarbonylalkyl" include
CH.sub.3C(.dbd.O)CH.sub.2CH(CH.sub.3),
CH.sub.3CH.sub.2C(.dbd.O)CH.sub.2CH.sub.2 and
(CH.sub.3).sub.2CHOC(.dbd.O)CH.sub.2.
[0026] The term "alkylcarbonylamino" denotes alkyl bonded to a
C(.dbd.O)NH moiety. Examples of "alkylcarbonylamino" include
CH.sub.3CH.sub.2C(.dbd.O)NH and
CH.sub.3CH.sub.2CH.sub.2C(.dbd.O)NH. "Alkylsulfonylamino" denotes
an NH radical substituted with alkylsulfonyl. Examples of
"alkylsulfonylamino" include CH.sub.3CH.sub.2S(.dbd.O).sub.2NH and
(CH.sub.3).sub.2CHS(.dbd.O).sub.2NH.
[0027] "Trialkylsilyl" includes 3 branched and/or straight-chain
alkyl radicals attached to and linked through a silicon atom, such
as trimethylsilyl, triethylsilyl and tert-butyldimethylsilyl.
[0028] "Hydroxyalkyl" denotes an alkyl group substituted with one
hydroxy group. Examples of "hydroxyalkyl" include
HOCH.sub.2CH.sub.2, CH.sub.3CH.sub.2(OH)CH and
HOCH.sub.2CH.sub.2CH.sub.2CH.sub.2.
[0029] The term "halogen", either alone or in compound words such
as "haloalkyl", or when used in descriptions such as "alkyl
substituted with halogen" includes fluorine, chlorine, bromine or
iodine. Further, when used in compound words such as "haloalkyl",
or when used in descriptions such as "alkyl substituted with
halogen" said alkyl may be partially or fully substituted with
halogen atoms which may be the same or different. Examples of
"haloalkyl" or "alkyl substituted with halogen" include F.sub.3C,
ClCH.sub.2, CF.sub.3CH.sub.2 and CF.sub.3CCl.sub.2. The terms
"halocycloalkyl", "haloalkoxy", "haloalkylthio", "haloalkylamino",
"haloalkylsulfinyl", "haloalkylsulfonyl", "haloalkenyl",
"haloalkynyl", and the like, are defined analogously to the term
"haloalkyl". Examples of "halocycloalkyl" include
2-chlorocyclopropyl, 2-fluorocyclobutyl, 3-bromocyclopentyl and
4-chorocyclohexyl. Examples of "haloalkoxy" include CF.sub.3O,
CCl.sub.3CH.sub.2O, HCF.sub.2CH.sub.2CH.sub.2O and
CF.sub.3CH.sub.2O. Examples of "haloalkylthio" include CCl.sub.3S,
CF.sub.3S, CCl.sub.3CH.sub.2S and ClCH.sub.2CH.sub.2CH.sub.2S.
Examples of "haloalkylamino" include CF.sub.3(CH.sub.3)CHNH,
(CF.sub.3).sub.2CHNH and CH.sub.2ClCH.sub.2NH. Examples of
"haloalkylsulfinyl" include CF.sub.3S(.dbd.O), CCl.sub.3S(.dbd.O),
CF.sub.3CH.sub.2S(.dbd.O) and CF.sub.3CF.sub.2S(.dbd.O). Examples
of "haloalkylsulfonyl" include CF.sub.3S(.dbd.O).sub.2,
CCl.sub.3S(.dbd.O).sub.2, CF.sub.3CH.sub.2S(.dbd.O).sub.2 and
CF.sub.3CF.sub.2S(.dbd.O).sub.2. Examples of "haloalkenyl" include
(Cl).sub.2C.dbd.CHCH.sub.2 and CF.sub.3CH.sub.2CH.dbd.CHCH.sub.2.
Examples of "haloalkynyl" include HC.ident.CCHCl,
CF.sub.3C.ident.C, CCl.sub.3C.ident.C and
FCH.sub.2C.ident.CCH.sub.2. The term "halodialkyl", either alone or
in compound words such as "halodialkylamino", means at least one of
the two alkyl groups is substituted with at least one halogen atom,
and independently each halogenated alkyl group may be partially or
fully substituted with halogen atoms which may be the same or
different. Examples of "halodialkylamino" include
(BrCH.sub.2CH.sub.2).sub.2N and
BrCH.sub.2CH.sub.2(ClCH.sub.2CH.sub.2)N.
[0030] The total number of carbon atoms in a substituent group is
indicated by the "C.sub.i-C.sub.j" prefix where i and j are numbers
from 1 to 9. For example, C.sub.1-C.sub.4 alkylsulfonyl designates
methylsulfonyl through butylsulfonyl; C.sub.2 alkoxyalkyl
designates CH.sub.3OCH.sub.2; C.sub.3 alkoxyalkyl designates, for
example, CH.sub.3CH(OCH.sub.3), CH.sub.3OCH.sub.2CH.sub.2 or
CH.sub.3CH.sub.2OCH--; and C.sub.4 alkoxyalkyl designates the
various isomers of an alkyl group substituted with an alkoxy group
containing a total of four carbon atoms, examples including
CH.sub.3CH.sub.2CH.sub.2OCH.sub.2 and
CH.sub.3CH.sub.2OCH.sub.2CH.sub.2.
[0031] When a compound is substituted with a substituent bearing a
subscript that indicates the number of said substituents can vary,
then when the number of said substituents is greater than 1, said
substituents are independently selected from the group of defined
substituents (e.g., (R.sup.1).sub.n wherein n is 1, 2, 3, 4 or
5).
[0032] Compounds of this invention can exist as one or more
stereoisomers. The various stereoisomers include enantiomers,
diastereomers, atropisomers and geometric isomers. Of note are
atropisomers, which are conformational isomers that occur when
rotation about a single bond in a molecule is restricted as a
result of steric interaction with other parts of the molecule and
the substituents at both ends of the single bond are unsymmetrical.
In the present invention, atropisomerism occurs at a single bond in
Formula 1 when the rotational barrier is high enough (about
.DELTA.G>25 kcal mol.sup.-1) that separation of isomers at
ambient temperature becomes possible. One skilled in the art will
appreciate that one atropisomer may be more active and/or may
exhibit beneficial effects when enriched relative to the other
atropisomer or when separated from the other atropisomer.
Additionally, the skilled artisan knows how to separate, enrich,
and/or to selectively prepare said atropisomers. A detailed
description of atropisomers can be found in March, Advanced Organic
Chemistry, 101-102, 4.sup.th Ed. 1992 and Gawronski et al,
Chirality 2002, 14, 689-702. This invention includes compounds or
compositions that are enriched in an atropisomer of Formula 1
compared to other atropisomers of the compounds. Also included are
the essentially pure atropisomers of compounds of Formula 1.
[0033] Compounds of this invention can exist as one or more
conformational isomers due to restricted rotation about an amide
bond (e.g., wherein R.sup.1 is alkylaminocarbonyl or
dialkylaminocarbonyl). This invention comprises mixtures of
conformational isomers. In addition, this invention includes
compounds that are enriched in one conformer relative to
others.
[0034] One skilled in the art will recognize that tertiary amines
can form N-oxides. Synthetic methods for the preparation of
N-oxides of tertiary amines are very well known by one skilled in
the art including the oxidation of tertiary amines with peroxy
acids such as peracetic and m-chloroperbenzoic acid (MCPBA),
hydrogen peroxide, alkyl hydroperoxides such as t-butyl
hydroperoxide, sodium perborate, and dioxiranes such as
dimethyldioxirane. These methods for the preparation of N-oxides
have been extensively described and reviewed in the literature, see
for example: T. L. Gilchrist in Comprehensive Organic Synthesis,
vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and
B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp
18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R.
Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry,
vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M.
Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol.
9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic
Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in
Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A.
J. Boulton, Eds., Academic Press.
[0035] One skilled in the art recognizes that because in the
environment and under physiological conditions salts of chemical
compounds are in equilibrium with their corresponding nonsalt
forms, salts share the biological utility of the nonsalt forms.
Thus a wide variety of salts of the compounds of Formula 1 are
useful for control of plant diseases caused by fungal plant
pathogens (i.e. are agriculturally suitable). The salts of the
compounds of Formula 1 include acid-addition salts with inorganic
or organic acids such as hydrobromic, hydrochloric, nitric,
phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic,
malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic
or valeric acids. When a compound of Formula 1 contains an acidic
moiety such as a phenol, salts also include those formed with
organic or inorganic bases such as pyridine, triethylamine or
ammonia, or amides, hydrides, hydroxides or carbonates of sodium,
potassium, lithium, calcium, magnesium or barium. Accordingly, the
present invention comprises compounds selected from Formula 1,
N-oxides and agriculturally suitable salts thereof.
[0036] Compounds selected from Formula 1, geometric and
stereoisomers, N-oxides, and salts thereof, typically exist in more
than one form, and Formula 1 thus includes all crystalline and
non-crystalline forms of the compounds that Formula 1 represents.
Non-crystalline forms include embodiments which are solids such as
waxes and gums as well as embodiments which are liquids such as
solutions and melts. Crystalline forms include embodiments which
represent essentially a single crystal type and embodiments which
represent a mixture of polymorphs (i.e. different crystalline
types). The term "polymorph" refers to a particular crystalline
form of a chemical compound that can crystallize in different
crystalline forms, these forms having different arrangements and/or
conformations of the molecules in the crystal lattice. Although
polymorphs can have the same chemical composition, they can also
differ in composition due the presence or absence of
co-crystallized water or other molecules, which can be weakly or
strongly bound in the lattice. Polymorphs can differ in such
chemical, physical and biological properties as crystal shape,
density, hardness, color, chemical stability, melting point,
hygroscopicity, suspensibility, dissolution rate and biological
availability. One skilled in the art will appreciate that a
polymorph of a compound represented by Formula 1 can exhibit
beneficial effects (e.g., suitability for preparation of useful
formulations, improved biological performance) relative to another
polymorph or a mixture of polymorphs of the same compound
represented by Formula 1. Preparation and isolation of a particular
polymorph of a compound represented by Formula 1 can be achieved by
methods known to those skilled in the art including, for example,
crystallization using selected solvents and temperatures.
[0037] Embodiments of the present invention as described in the
Summary of the Invention include those described below. In the
following Embodiments, Formula 1 includes geometric and
stereoisomers, N-oxides, and salts thereof, and reference to "a
compound of Formula 1" includes the definitions of substituents
specified in the Summary of the Invention unless further defined in
the Embodiments. [0038] Embodiment 1. A compound of Formula 1
wherein each R.sup.1 is independently halogen, cyano, nitro,
C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6
alkynyl, C.sub.1-C.sub.6 haloalkyl, C.sub.2-C.sub.6 alkoxyalkyl,
C.sub.2-C.sub.6 alkylcarbonyl, C.sub.2-C.sub.6 alkoxycarbonyl,
C.sub.2-C.sub.6 alkylaminocarbonyl, C.sub.3-C.sub.8
dialkylaminocarbonyl, C.sub.2-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6
hydroxyalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkylthio,
C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 alkylsulfonyl,
C.sub.1-C.sub.6 alkylamino, C.sub.2-C.sub.6 dialkylamino or
C.sub.2-C.sub.6 alkylcarbonylamino. [0039] Embodiment 2. A compound
of Embodiment 1 wherein each R.sup.1 is independently halogen,
C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6
haloalkyl, C.sub.2-C.sub.6 alkylcarbonyl, C.sub.2-C.sub.6
alkoxycarbonyl or C.sub.1-C.sub.6 alkoxy. [0040] Embodiment 3. A
compound of Embodiment 2 wherein each R.sup.1 is independently
halogen, C.sub.1-C.sub.6 alkyl or C.sub.1-C.sub.6 alkoxy. [0041]
Embodiment 4. A compound of Embodiment 3 wherein each R.sup.1 is
independently halogen. [0042] Embodiment 4a. A compound of
Embodiment 4 wherein each R.sup.1 is independently F or Cl. [0043]
Embodiment 5. A compound of Formula 1 or any one of Embodiments 1
through 4a wherein R.sup.2 is F. [0044] Embodiment 6. A compound of
Formula 1 or any one of Embodiments 1 through 5 wherein R.sup.3 is
Cl, F, Br or methoxy. [0045] Embodiment 7. A compound of Embodiment
6 wherein R.sup.3 is F or methoxy. [0046] Embodiment 8. A compound
of Embodiment 7 wherein R.sup.3 is methoxy. [0047] Embodiment 9. A
compound of Embodiment 7 wherein R.sup.3 is F. [0048] Embodiment
10. A compound of Formula 1 or any one of Embodiments 1 through 9
wherein the R.sup.3 substituent is attached at the para position.
[0049] Embodiment 11. A compound of Formula 1 or any one of
Embodiments 1 through 10 wherein R.sup.4 is H, Cl, F or Br. [0050]
Embodiment 12. A compound of Embodiment 11 wherein R.sup.4 is Cl or
F. [0051] Embodiment 13. A compound of Embodiment 12 wherein
R.sup.4 is Cl. [0052] Embodiment 14. A compound of Formula 1 or any
one of Embodiments 1 through 13 wherein n is 0 or 1. [0053]
Embodiment 15. A compound of Embodiment 14 wherein n is 1. [0054]
Embodiment 16. A compound of Embodiment 14 wherein n is 0.
[0055] Embodiments of this invention, including Embodiments 1-16
above as well as any other embodiments described herein, can be
combined in any manner, and the descriptions of variables in the
embodiments pertain not only to the compounds of Formula 1 but also
to the starting compounds and intermediate compounds useful for
preparing the compounds of Formula 1. In addition, embodiments of
this invention, including Embodiments 1-16 above as well as any
other embodiments described herein, and any combination thereof,
pertain to the compositions and methods of the present
invention.
[0056] Combinations of Embodiments 1-16 are illustrated by:
[0057] Embodiment A. A compound of Formula 1 wherein [0058] each
R.sup.1 is independently halogen, cyano, nitro, C.sub.1-C.sub.6
alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl,
C.sub.1-C.sub.6 haloalkyl, C.sub.2-C.sub.6 alkoxyalkyl,
C.sub.2-C.sub.6 alkylcarbonyl, C.sub.2-C.sub.6 alkoxycarbonyl,
C.sub.2-C.sub.6 alkylaminocarbonyl, C.sub.3-C.sub.8
dialkylaminocarbonyl, C.sub.2-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6
hydroxyalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkylthio,
C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 alkylsulfonyl,
C.sub.1-C.sub.6 alkylamino, C.sub.2-C.sub.6 dialkylamino or
C.sub.2-C.sub.6 alkylcarbonylamino.
[0059] Embodiment B. A compound of Embodiment A wherein [0060] each
R.sup.1 is independently is halogen, C.sub.1-C.sub.6 alkyl,
C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 haloalkyl, C.sub.2-C.sub.6
alkylcarbonyl, C.sub.2-C.sub.6 alkoxycarbonyl or C.sub.1-C.sub.6
alkoxy; [0061] R.sup.3 is Cl, F, Br or methoxy; and [0062] R.sup.4
is H, Cl, F or Br.
[0063] Embodiment C. A compound of Embodiment B wherein each
R.sup.1 is independently halogen, C.sub.1-C.sub.6 alkyl or
C.sub.1-C.sub.6 alkoxy; [0064] R.sup.3 is F or methoxy; and [0065]
R.sup.4 is Cl or F.
[0066] Embodiment D. A compound of Embodiment C wherein [0067]
R.sup.2 is F; [0068] R.sup.3 is F or methoxy; and [0069] n is 0 or
1.
[0070] Embodiment E. A compound of Embodiment D wherein [0071]
R.sup.3 is attached at the para position.
[0072] Embodiment F. A compound of Embodiment E wherein [0073]
R.sup.3 is F.
[0074] Embodiment G. A compound of Embodiment E wherein [0075]
R.sup.3 is methoxy.
[0076] This invention provides a fungicidal composition comprising
a compound of Formula 1 (including all geometric and stereoisomers,
N-oxides, and salts thereof), and at least one other fungicide. Of
note as embodiments of such compositions are compositions
comprising a compound corresponding to any of the compound
embodiments described above.
[0077] This invention provides a fungicidal composition comprising
a compound of Formula 1 (including all geometric and stereoisomers,
N-oxides, and salts thereof), and at least one additional component
selected from the group consisting of surfactants, solid diluents
and liquid diluents. Of note as embodiments of such compositions
are compositions comprising a compound corresponding to any of the
compound embodiments described above.
[0078] This invention provides a method for controlling plant
diseases caused by fungal plant pathogens comprising applying to
the plant or portion thereof, or to the plant seed, a fungicidally
effective amount of a compound of Formula 1 (including all
geometric and stereoisomers, N-oxides, and salts thereof). Of note
as embodiments of such methods are methods comprising applying a
fungicidally effective amount of a compound corresponding to any of
the compound embodiments described above. Of particular notes are
embodiments where the compounds are applied as compositions of this
invention.
[0079] One or more of the following methods and variations as
described in Schemes 1-6 can be used to prepare the compounds of
Formula 1. The definitions of R.sup.1, R.sup.2, R.sup.3, R.sup.4
and n in the compounds of Formulae 1-11 below are as defined above
in the Summary of the Invention unless otherwise noted.
[0080] Compounds of Formula 1 can be prepared by reacting imines of
Formula 2 with phenylpropiolate derivatives of Formula 3 as shown
in Scheme 1. The reaction is typically conducted in a suitable
solvent, such as xylenes, toluene, chlorobenzene, and mixtures
thereof. Addition of an acid-catalyst such as p-toluenesulfonic
acid or a Lewis acid such as trifluoroacetic acid, aluminum
chloride or aluminum bromide can facilitate the reaction. The
reaction is typically conducted at a temperature between about 20
and 200.degree. C. For representative procedures see Barluenga et
al., Synthetic Communications 1983, 13, 411-417, U.S. Pat. No.
4,757,081 and European Patent 304057. Also Step C of Example 1
illustrates the method of Scheme 1.
##STR00005##
[0081] As shown below in Scheme 2, imines of Formula 2 can be
prepared by reacting ketones of Formula 4 with anilines of Formula
5 under dehydrative conditions such as heating in toluene or
xylenes with use of a Dean-Stark trap or in presence of molecular
sieves to remove water formed in the reaction. An acid catalyst can
be added to the reaction mixture to promote elimination of water.
Examples of suitable acid catalyst include p-toluenesulfonic acid,
acetic acid or formic acid, or a Lewis Acid such titanium
tetrachloride. For representative procedures see Strekowski et al.,
Tetrahedron Letters 1989, 30(39), 5197-5160; Rhee et al., Synlett
2003, (1), 112-114 and U.S. Pat. No. 1,938,890. Also, Step B of
Example 1 illustrates the preparation of a compound of Formula
2.
##STR00006##
[0082] Compounds of Formula 3 can be prepared by a number of
methods known in the art. According to the method of Scheme 3, an
alkynylzinc intermediate is first generated in situ by treatment of
an alkyne of Formula 6 with lithium diisopropylamide (LDA) followed
by zinc bromide or zinc chloride. Treatment of the alkynylzinc
intermediate with a phenyl halide of Formula 7 in the presence of a
palladium catalyst such as tetrakis(triphenylphosphine)palladium
(Pd(PPd.sub.3).sub.4) and a solvent such a tetrahydrofuran at a
temperature between about -78.degree. C. and room temperature
provides the corresponding compound of Formula 3. For references
illustrating this procedure and related methods see Anastasia et
al., Organic Letters 2001, 3, 3111-3113; King et al., Journal of
the Chemical Society., Chemical Communications 1977, (19), 683-684;
and King et al., Journal of Organic Chemistry 1978, 43(2), 358-360.
Also, Step A of Example 1 illustrates the preparation of a compound
of Formula 3 by the method of Scheme 3.
##STR00007##
[0083] Alternatively, compounds of Formula 3 can be prepared via a
cross-coupling reaction of phenylboronic acids and alkynes
according to the procedure by Zou et al., Tetrahedron Letters 2003,
44, 8709-8711.
[0084] Anilines of Formula 5 are commercially available and can be
readily synthesized by methods known in the art; see, for example,
Sun et al., Journal of Organic Chemistry 1997, 62, 6469-6475 and
PCT Patent Publication WO 2003/064398.
[0085] Compounds of Formula 4 can be conveniently prepared via a
Friedel-Crafts acylation reaction as shown in Scheme 4. In this
method a compound of Formula 8 is reacted with propionyl chloride
in the presence of aluminum chloride. The reaction can be run in a
solvent such methylene chloride or chloroform, or without solvent
other than the compound of Formula 8 and propionyl chloride. The
reaction is typically carried out at a temperature between about
0.degree. C. and the reflux temperature of the reaction mixture.
For representative procedures see Joshi et al., Journal of Fluorine
Chemistry 1980, 15, 245-52; Watanabe et al., Bioorganic &
Medicinal Chemistry Letters 2008, 185, 1478-1483 and Xu et al.,
Synthetic Communications 2005, 35, 2345-2353.
##STR00008##
[0086] Alternatively, compounds of Formula 4 can be prepared as
shown in Scheme 5. In this method an organometallic reagent of
Formula 9 wherein M is MgX.sup.2, Li or ZnX.sup.2 and X.sup.2 is
Cl, Br or I is contacted with an electrophile of Formula 10 wherein
Lg is a leaving group such as halogen, resulting in the
introduction of a propionyl group onto Formula 9 to provide a
compound of Formula 4.
[0087] Some organometallic reagents of Formula 9 are commercially
available (e.g., phenyl Grignard reagents); also many known methods
in the art for preparing organometallic reagents involving
metallation with a metalating agent such as n-butyllithium
(n-BuLi), lithium diisopropylamide (LDA) or a Grignard reagent
(e.g., EtMgBr) can be used to prepare compounds of Formula 9. For
representative procedures see Watanabe et al., Bioorganic &
Medicinal Chemistry Letters 2008, 185, 1478-1483.
##STR00009##
[0088] Compounds of Formula 1 can also be prepared by condensation
of triketones of Formula 11 with anilines of Formula 5 as shown in
Scheme 6. Typically the reaction is run in a solvent such as
toluene, xylenes, chlorobenzene or N,N-dimethylformamide, at a
temperature between about room temperature and 200.degree. C. An
acid catalyst can be added to the reaction mixture to promote
elimination of water. Examples of suitable acid catalysts include,
sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, acetic
acid, formic acid, or a Lewis acid such titanium tetrachloride or
aluminum chloride. Use of a Dean-Stark trap or molecular sieves can
be used to remove water formed in the reaction. For representative
references describing the method of Scheme 5 see U.S. Pat. No.
4,757,081 and European Patent 304057.
##STR00010##
[0089] Compounds of Formula 11 can be prepared by a number of
procedures. For a particularly useful procedure see Japanese Patent
Application Publication 03120262.
[0090] Without further elaboration, it is believed that one skilled
in the art using the preceding description can utilize the present
invention to its fullest extent. The following Examples are,
therefore, to be construed as merely illustrative, and not limiting
of the disclosure in any way whatsoever. Steps in the following
Examples illustrate a procedure for each step in an overall
synthetic transformation, and the starting material for each step
may not have necessarily been prepared by a particular preparative
run whose procedure is described in other Examples or Steps.
Percentages are by weight except for chromatographic solvent
mixtures or where otherwise indicated. Parts and percentages for
chromatographic solvent mixtures are by volume unless otherwise
indicated. .sup.1H NMR spectra are reported in ppm downfield from
tetramethylsilane; "s" means singlet, "d" means doublet, "t" means
triplet, "q" means quartet, "m" means multiplet.
Example 1
Preparation of
1-(2-chloro-3-5-dimethoxyphenyl)-6-(4-fluorophenyl)-3-methyl-2-(2,4,6-tri-
fluorophenyl)-4-(1H)-pyridinone
Step A: Preparation of ethyl 4-fluorophenylpropynoate
[0091] To a stirred mixture of diisopropylamine (6.20 g, 61.3 mmol)
in tetrahydrofuran at -78.degree. C. under an argon atmosphere (15
mL), n-butyllithium (3.92 g, 61.2 mmol, 1.6 M in hexanes) was
added. The reaction mixture was maintained under an argon
atmosphere and stirred for 20 minutes at -50.degree. C. The
reaction mixture was cooled to -78.degree. C., and a solution of
ethyl propiolate (5.0 g, 51 mmol) in tetrahydrofuran (15 mL) was
added. After stirring for 20 minutes at -78.degree. C., a mixture
of zinc chloride (8.34 g, 61.2 mmol) in tetrahydrofuran (20 mL) was
added to the reaction mixture and stirring was continued at
-78.degree. C.
[0092] In another reaction vessel,
tetrakis(triphenylphosphine)palladium (Pd(PPd.sub.3).sub.4) (2.9 g,
2.5 mmol) was added to a mixture of 1-fluoro-4-iodobenzene (11.32
g, 51.0 mmol) in tetrahydrofuran (25 mL). The reaction mixture was
maintained under an argon atmosphere, stirred for 15 minutes, then
cooled to -78.degree. C., and the reaction mixture formed from
ethyl 4-fluorophenylpropynoate was added via syringe. After the
addition was complete, the reaction mixture was allowed to slowly
warm to room temperature. After 1.3 h, saturated aqueous ammonium
chloride solution was added to the reaction mixture, and the
mixture was extracted with ethyl acetate. The organic layer was
washed with water and saturated aqueous sodium chloride solution,
dried (Na.sub.2SO.sub.4), filtered and concentrated. The resulting
residue was purified by column chromatography on silica gel (using
2% ethyl acetate-petroleum ether as eluant) to provide the title
compound as a pale yellow solid (5 g).
[0093] .sup.1H NMR (CDCl.sub.3): .delta. 6.74-6.67 (m, 2H), 2.87
(q, J=7.2 Hz, 2H), 1.19 (t, J=7.2 Hz, 3H).
Step B: Preparation of
2-chloro-3,5-dimethoxy-N-[1-(2,4,6-trifluorophenyl)propylidene]benzenamin-
e
[0094] A mixture of 1-(2,4,6-trifluorophenyl)-1-propanone (7.0 g,
37.2 mmol), 2-chloro-3,5-dimethoxybenzenamine (see European Patent
1333028 for a method of preparation) (6.96 g, 37.1 mmol) and
p-toluenesulfonic acid (1.41 g, 8.2 mmol) in toluene (80 mL) was
heated at reflux with use of a Dean-Stark trap to remove water.
After 20 h, the reaction mixture was cooled to room temperature and
diluted with ethyl acetate. The organic layer was washed with
water, sulfuric acid (1 N), water and saturated aqueous sodium
chloride solution. The organic layer was dried (Na.sub.2SO.sub.4),
filtered and concentrated to provide the title compound (10 g)
which was used without further purification in Step C below.
Step C: Preparation of
1-(2-chloro-3-5-dimethoxyphenyl)-6-(4-fluorophenyl)-3-methyl-2-(2,4,6-tri-
fluorophenyl)-4-(1H)-pyridinone
[0095] A mixture of ethyl 4-fluorophenylpropynoate (i.e. the
product of Step A) (2.68 g, 14.0 mmol),
2-chloro-3,5-dimethoxy-N-[1-(2,4,6-trifluorophenyl)propylidene]benzenamin-
e (i.e. the product of Step B) (5.0 g, 13.9 mmol) and aluminum
chloride (2.79 g, 21.1 mmol) in toluene (160 mL) was heated at
reflux for 16 h. The reaction mixture was cooled, and poured onto
ice, and the mixture was extracted with chloroform. The chloroform
layer was washed with sulfuric acid (1 N), sodium hydroxide
solution (5% in water), dried (Na.sub.2SO.sub.4), filtered and
concentrated. The resulting residue (7 g) was purified by column
chromatography to provide a solid which was further purified by
reverse phase HPLC to provide the title compound, a compound of the
present invention, as an off-white solid (65 mg).
[0096] .sup.1H NMR (CDCl.sub.3): .delta. 7.24-7.23 (m, 2H), 6.88
(t, J=8.6 Hz, 2H), 6.62-6.56 (m, 3H), 6.38-6.37 (m, 1H), 6.23 (d,
J=2.4 Hz, 1H), 3.7 (s, 3H), 3.65 (s, 3H), 1.90 (s, 3H).
[0097] By the procedures described herein together with methods
known in the art, the following compounds of Table 1 can be
prepared. The following abbreviations are used in the Tables which
follow: c means cyclo, Me means methyl, Pr means propyl, c-Pr means
cyclopropyl, OMe means methoxy, SMe means methylthio, CN means
cyano, means phenyl, NO.sub.2 means nitro, S(O)Me means
methylsulfinyl, and S(O).sub.2Me means methylsulfonyl. In the
following table a dash ("-") in the (R.sup.1).sub.n indicates n is
0 and hydrogen is present at all available positions.
TABLE-US-00001 TABLE 1 ##STR00011## R.sup.2 is F, R.sup.3 is
R.sup.2 is F, R.sup.3 is R.sup.2 is F, R.sup.3 is R.sup.2 is F,
R.sup.3 is 4-F and R.sup.4 4-F and R.sup.4 4-OMe and R.sup.4 4-OMe
and R.sup.4 is H. is Cl. is H. is Cl. (R.sup.1).sub.n
(R.sup.1).sub.n (R.sup.1).sub.n (R.sup.1).sub.n -- -- -- -- 2-F 2-F
2-F 2-F 3-F 3-F 3-F 3-F 4-F 4-F 4-F 4-F 2-Cl 2-Cl 2-Cl 2-Cl 3-Cl
3-Cl 3-Cl 3-Cl 4-Cl 4-Cl 4-Cl 4-Cl 2-Br 2-Br 2-Br 2-Br 3-Br 3-Br
3-Br 3-Br 4-Br 4-Br 4-Br 4-Br 2-I 2-I 2-I 2-I 3-I 3-I 3-I 3-I 4-I
4-I 4-I 4-I 2,4-di-F 2,4-di-F 2,4-di-F 2,4-di-F 2-F, 4-Cl 2-F, 4-Cl
2-F, 4-Cl 2-F, 4-Cl 2-Cl, 4-F 2-Cl, 4-F 2-Cl, 4-F 2-Cl, 4-F
2-CF.sub.3 2-CF.sub.3 2-CF.sub.3 2-CF.sub.3 4-CF.sub.3 4-CF.sub.3
4-CF.sub.3 4-CF.sub.3 2-F, 4-CF.sub.3 2-F, 4-CF.sub.3 2-F,
4-CF.sub.3 2-F, 4-CF.sub.3 2-Me 2-Me 2-Me 2-Me 4-Me 4-Me 4-Me 4-Me
2-OMe 2-OMe 2-OMe 2-OMe 4-OMe 4-OMe 4-OMe 4-OMe 2-SMe 2-SMe 2-SMe
2-SMe 4-SMe 4-SMe 4-SMe 4-SMe 4-SCF.sub.3 4-SCF.sub.3 4-SCF.sub.3
4-SCF.sub.3 2-S(O)Me 2-S(O)Me 2-S(O)Me 2-S(O)Me 4-S(O)Me 4-S(O)Me
4-S(O)Me 4-S(O)Me 4-S(O).sub.2Me 4-S(O).sub.2Me 4-S(O).sub.2Me
4-S(O).sub.2Me 2-CN 2-CN 2-CN 2-CN 3-CN 3-CN 3-CN 3-CN 4-CN 4-CN
4-CN 4-CN 2-F, 4-CN 2-F, 4-CN 2-F, 4-CN 2-F, 4-CN 4-c-Pr 4-c-Pr
4-c-Pr 4-c-Pr 2-C(.dbd.O)Me 2-C(.dbd.O)Me 2-C(.dbd.O)Me
2-C(.dbd.O)Me 4-CO.sub.2Me 4-CO.sub.2Me 4-CO.sub.2Me 4-CO.sub.2Me
3-OCH.sub.2OMe 3-OCH.sub.2OMe 3-OCH.sub.2OMe 3-OCH.sub.2OMe
4-C(.dbd.O)NMe.sub.2 4-C(.dbd.O)NMe.sub.2 4-C(.dbd.O)NMe.sub.2
4-C(.dbd.O)NMe.sub.2 4-S(O).sub.2NMe.sub.2 4-S(O).sub.2NMe.sub.2
4-S(O).sub.2NMe.sub.2 4-S(O).sub.2NMe.sub.2 3-NO.sub.2 3-NO.sub.2
3-NO.sub.2 3-NO.sub.2 R.sup.2 is Cl, R.sup.3 is R.sup.2 is Cl,
R.sup.3 is R.sup.2 is Cl, R.sup.3 is R.sup.2 is Cl, R.sup.3 is 4-F
and R.sup.4 4-F and R.sup.4 4-OMe and R.sup.4 4-OMe and R.sup.4 is
H. is Cl. is H. is Cl. (R.sup.1).sub.n (R.sup.1).sub.n
(R.sup.1).sub.n (R.sup.1).sub.n -- -- -- -- 2-F 2-F 2-F 2-F 3-F 3-F
3-F 3-F 4-F 4-F 4-F 4-F 2-Cl 2-Cl 2-Cl 2-Cl 3-Cl 3-Cl 3-Cl 3-Cl
4-Cl 4-Cl 4-Cl 4-Cl 2-Br 2-Br 2-Br 2-Br 3-Br 3-Br 3-Br 3-Br 4-Br
4-Br 4-Br 4-Br 2-I 2-I 2-I 2-I 3-I 3-I 3-I 3-I 4-I 4-I 4-I 4-I
2,4-di-F 2,4-di-F 2,4-di-F 2,4-di-F 2-F, 4-Cl 2-F, 4-Cl 2-F, 4-Cl
2-F, 4-Cl 2-Cl, 4-F 2-Cl, 4-F 2-Cl, 4-F 2-Cl, 4-F 2-CF.sub.3
2-CF.sub.3 2-CF.sub.3 2-CF.sub.3 4-CF.sub.3 4-CF.sub.3 4-CF.sub.3
4-CF.sub.3 2-F, 4-CF.sub.3 2-F, 4-CF.sub.3 2-F, 4-CF.sub.3 2-F,
4-CF.sub.3 2-Me 2-Me 2-Me 2-Me 4-Me 4-Me 4-Me 4-Me 2-OMe 2-OMe
2-OMe 2-OMe 4-OMe 4-OMe 4-OMe 4-OMe 2-SMe 2-SMe 2-SMe 2-SMe 4-SMe
4-SMe 4-SMe 4-SMe 4-SCF.sub.3 4-SCF.sub.3 4-SCF.sub.3 4-SCF.sub.3
2-S(O)Me 2-S(O)Me 2-S(O)Me 2-S(O)Me 4-S(O)Me 4-S(O)Me 4-S(O)Me
4-S(O)Me 4-S(O).sub.2Me 4-S(O).sub.2Me 4-S(O).sub.2Me
4-S(O).sub.2Me 2-CN 2-CN 2-CN 2-CN 3-CN 3-CN 3-CN 3-CN 4-CN 4-CN
4-CN 4-CN 2-F, 4-CN 2-F, 4-CN 2-F, 4-CN 2-F, 4-CN 4-c-Pr 4-c-Pr
4-c-Pr 4-c-Pr 2-C(.dbd.O)Me 2-C(.dbd.O)Me 2-C(.dbd.O)Me
2-C(.dbd.O)Me 4-CO.sub.2Me 4-CO.sub.2Me 4-CO.sub.2Me 4-CO.sub.2Me
3-OCH.sub.2OMe 3-OCH.sub.2OMe 3-OCH.sub.2OMe 3-OCH.sub.2OMe
4-C(.dbd.O)NMe.sub.2 4-C(.dbd.O)NMe.sub.2 4-C(.dbd.O)NMe.sub.2
4-C(.dbd.O)NMe.sub.2 4-S(O).sub.2NMe.sub.2 4-S(O).sub.2NMe.sub.2
4-S(O).sub.2NMe.sub.2 4-S(O).sub.2NMe.sub.2 3-NO.sub.2 3-NO.sub.2
3-NO.sub.2 3-NO.sub.2 R.sup.2 is F, R.sup.3 is R.sup.2 is F,
R.sup.3 is R.sup.2 is F, R.sup.3 is R.sup.2 is F, R.sup.3 is 3-F
and R.sup.4 3-F and R.sup.4 4-Cl and R.sup.4 4-Cl and R.sup.4 is H.
is Cl. is H. is Cl. (R.sup.1).sub.n (R.sup.1).sub.n (R.sup.1).sub.n
(R.sup.1).sub.n 2-F 2-F 2-F 2-F 3-F 3-F 3-F 3-F 4-F 4-F 4-F 4-F
2-Cl 2-Cl 2-Cl 2-Cl 3-Cl 3-Cl 3-Cl 3-Cl 4-Cl 4-Cl 4-Cl 4-Cl 2-Br
2-Br 2-Br 2-Br 3-Br 3-Br 3-Br 3-Br 4-Br 4-Br 4-Br 4-Br 2-I 2-I 2-I
2-I 3-I 3-I 3-I 3-I 4-I 4-I 4-I 4-I 2,4-di-F 2,4-di-F 2,4-di-F
2,4-di-F 2-F, 4-Cl 2-F, 4-Cl 2-F, 4-Cl 2-F, 4-Cl 2-Cl, 4-F 2-Cl,
4-F 2-Cl, 4-F 2-Cl, 4-F 2-CF.sub.3 2-CF.sub.3 2-CF.sub.3 2-CF.sub.3
4-CF.sub.3 4-CF.sub.3 4-CF.sub.3 4-CF.sub.3 2-F, 4-CF.sub.3 2-F,
4-CF.sub.3 2-F, 4-CF.sub.3 2-F, 4-CF.sub.3 2-Me 2-Me 2-Me 2-Me 4-Me
4-Me 4-Me 4-Me 2-OMe 2-OMe 2-OMe 2-OMe 4-OMe 4-OMe 4-OMe 4-OMe
2-SMe 2-SMe 2-SMe 2-SMe 4-SMe 4-SMe 4-SMe 4-SMe 4-SCF.sub.3
4-SCF.sub.3 4-SCF.sub.3 4-SCF.sub.3 2-S(O)Me 2-S(O)Me 2-S(O)Me
2-S(O)Me 4-S(O)Me 4-S(O)Me 4-S(O)Me 4-S(O)Me 4-S(O).sub.2Me
4-S(O).sub.2Me 4-S(O).sub.2Me 4-S(O).sub.2Me 2-CN 2-CN 2-CN 2-CN
3-CN 3-CN 3-CN 3-CN 4-CN 4-CN 4-CN 4-CN 2-F, 4-CN 2-F, 4-CN 2-F,
4-CN 2-F, 4-CN 4-c-Pr 4-c-Pr 4-c-Pr 4-c-Pr 2-C(.dbd.O)Me
2-C(.dbd.O)Me 2-C(.dbd.O)Me 2-C(.dbd.O)Me 4-CO.sub.2Me 4-CO.sub.2Me
4-CO.sub.2Me 4-CO.sub.2Me 3-OCH.sub.2OMe 3-OCH.sub.2OMe
3-OCH.sub.2OMe 3-OCH.sub.2OMe 4-C(.dbd.O)NMe.sub.2
4-C(.dbd.O)NMe.sub.2 4-C(.dbd.O)NMe.sub.2 4-C(.dbd.O)NMe.sub.2
4-S(O).sub.2NMe.sub.2 4-S(O).sub.2NMe.sub.2 4-S(O).sub.2NMe.sub.2
4-S(O).sub.2NMe.sub.2 3-NO.sub.2 3-NO.sub.2 3-NO.sub.2 3-NO.sub.2
R.sup.2 is Cl, R.sup.3 is R.sup.2 is Cl, R.sup.3 is R.sup.2 is Cl,
R.sup.3 is R.sup.2 is Cl, R.sup.3 is 3-F and R.sup.4 3-F and
R.sup.4 4-Cl; R.sup.4 4-Cl and R.sup.4 is H. is Cl. is H. is Cl.
(R.sup.1).sub.n (R.sup.1).sub.n (R.sup.1).sub.n (R.sup.1).sub.n --
-- -- -- 2-F 2-F 2-F 2-F 3-F 3-F 3-F 3-F 4-F 4-F 4-F 4-F 2-Cl 2-Cl
2-Cl 2-Cl 3-Cl 3-Cl 3-Cl 3-Cl 4-Cl 4-Cl 4-Cl 4-Cl 2-Br 2-Br 2-Br
2-Br 3-Br 3-Br 3-Br 3-Br 4-Br 4-Br 4-Br 4-Br 2-I 2-I 2-I 2-I 3-I
3-I 3-I 3-I 4-I 4-I 4-I 4-I 2,4-di-F 2,4-di-F 2,4-di-F 2,4-di-F
2-F, 4-Cl 2-F, 4-Cl 2-F, 4-Cl 2-F, 4-Cl 2-Cl, 4-F 2-Cl, 4-F 2-Cl,
4-F 2-Cl, 4-F 2-CF.sub.3 2-CF.sub.3 2-CF.sub.3 2-CF.sub.3
4-CF.sub.3 4-CF.sub.3 4-CF.sub.3 4-CF.sub.3 2-F, 4-CF.sub.3 2-F,
4-CF.sub.3 2-F, 4-CF.sub.3 2-F, 4-CF.sub.3 2-Me 2-Me 2-Me 2-Me 4-Me
4-Me 4-Me 4-Me 2-OMe 2-OMe 2-OMe 2-OMe R.sup.2 is F, R.sup.3 is
R.sup.2 is F, R.sup.3 is R.sup.2 is F, R.sup.3 is R.sup.2 is F,
R.sup.3 is 3-Br and R.sup.4 3-Br and R.sup.4 4-Br and R.sup.4 4-Br
and R.sup.4 is H. is Cl. is H. is Cl. (R.sup.1).sub.n
(R.sup.1).sub.n (R.sup.1).sub.n (R.sup.1).sub.n 2-F 2-F 2-F 2-F 3-F
3-F 3-F 3-F 4-F 4-F 4-F 4-F 2-Cl 2-Cl 2-Cl 2-Cl 3-Cl 3-Cl 3-Cl 3-Cl
4-Cl 4-Cl 4-Cl 4-Cl 2-Br 2-Br 2-Br 2-Br 3-Br 3-Br 3-Br 3-Br 4-Br
4-Br 4-Br 4-Br 2-I 2-I 2-I 2-I 3-I 3-I 3-I 3-I 4-I 4-I 4-I 4-I
2,4-di-F 2,4-di-F 2,4-di-F 2,4-di-F 2-F, 4-Cl 2-F, 4-Cl 2-F, 4-Cl
2-F, 4-Cl 2-Cl, 4-F 2-Cl, 4-F 2-Cl, 4-F 2-Cl, 4-F 2-CF.sub.3
2-CF.sub.3 2-CF.sub.3 2-CF.sub.3 4-CF.sub.3 4-CF.sub.3 4-CF.sub.3
4-CF.sub.3 2-F, 4-CF.sub.3 2-F, 4-CF.sub.3 2-F, 4-CF.sub.3 2-F,
4-CF.sub.3 2-Me 2-Me 2-Me 2-Me 4-Me 4-Me 4-Me 4-Me 2-OMe 2-OMe
2-OMe 2-OMe R.sup.2 is Cl, R.sup.3 is R.sup.2 is Cl, R.sup.3 is
R.sup.2 is Cl, R.sup.3 is R.sup.2 is Cl, R.sup.3 is 5-F and R.sup.4
5-F and R.sup.4 5-Cl and R.sup.4 5-Cl and R.sup.4 is H. is Cl. is
H. is Cl. (R.sup.1).sub.n (R.sup.1).sub.n (R.sup.1).sub.n
(R.sup.1).sub.n 2-F 2-F 2-F 2-F 3-F 3-F 3-F 3-F 4-F 4-F 4-F 4-F
2-Cl 2-Cl 2-Cl 2-Cl 3-Cl 3-Cl 3-Cl 3-Cl 4-Cl 4-Cl 4-Cl 4-Cl 2-Br
2-Br 2-Br 2-Br 3-Br 3-Br 3-Br 3-Br 4-Br 4-Br 4-Br 4-Br 2-I 2-I 2-I
2-I 3-I 3-I 3-I 3-I 4-I 4-I 4-I 4-I 2,4-di-F 2,4-di-F 2,4-di-F
2,4-di-F 2-F, 4-Cl 2-F, 4-Cl 2-F, 4-Cl 2-F, 4-Cl 2-Cl, 4-F 2-Cl,
4-F 2-Cl, 4-F 2-Cl, 4-F 2-CF.sub.3 2-CF.sub.3 2-CF.sub.3 2-CF.sub.3
4-CF.sub.3 4-CF.sub.3 4-CF.sub.3 4-CF.sub.3 2-F, 4-CF.sub.3 2-F,
4-CF.sub.3 2-F, 4-CF.sub.3 2-F, 4-CF.sub.3 2-Me 2-Me 2-Me 2-Me 4-Me
4-Me 4-Me 4-Me 2-OMe 2-OMe 2-OMe 2-OMe
Formulation/Utility
[0098] A compound of Formula 1 of this invention will generally be
used as a fungicidal active ingredient in a composition, i.e.
formulation, with at least one additional component selected from
the group consisting of surfactants, solid diluents and liquid
diluents, which serve as a carrier. The formulation or composition
ingredients are selected to be consistent with the physical
properties of the active ingredient, mode of application and
environmental factors such as soil type, moisture and
temperature.
[0099] Useful formulations include both liquid and solid
compositions. Liquid compositions include solutions (including
emulsifiable concentrates), suspensions, emulsions (including
microemulsions and/or suspoemulsions) and the like, which
optionally can be thickened into gels. The general types of aqueous
liquid compositions are soluble concentrate, suspension
concentrate, capsule suspension, concentrated emulsion,
microemulsion and suspo-emulsion. The general types of nonaqueous
liquid compositions are emulsifiable concentrate, microemulsifiable
concentrate, dispersible concentrate and oil dispersion.
[0100] The general types of solid compositions are dusts, powders,
granules, pellets, pills, pastilles, tablets, filled films
(including seed coatings) and the like, which can be
water-dispersible ("wettable") or water-soluble. Films and coatings
formed from film-forming solutions or flowable suspensions are
particularly useful for seed treatment. Active ingredient can be
(micro)encapsulated and further formed into a suspension or solid
formulation; alternatively the entire formulation of active
ingredient can be encapsulated (or "overcoated"). Encapsulation can
control or delay release of the active ingredient. An emulsifiable
granule combines the advantages of both an emulsifiable concentrate
formulation and a dry granular formulation. High-strength
compositions are primarily used as intermediates for further
formulation.
[0101] Sprayable formulations are typically extended in a suitable
medium before spraying. Such liquid and solid formulations are
formulated to be readily diluted in the spray medium, usually
water. Spray volumes can range from about from about one to several
thousand liters per hectare, but more typically are in the range
from about ten to several hundred liters per hectare. Sprayable
formulations can be tank mixed with water or another suitable
medium for foliar treatment by aerial or ground application, or for
application to the growing medium of the plant. Liquid and dry
formulations can be metered directly into drip irrigation systems
or metered into the furrow during planting. Liquid and solid
formulations can be applied onto vegetable seeds as seed treatments
before planting to protect developing roots and other subterranean
plant parts and/or foliage through systemic uptake.
[0102] The formulations will typically contain effective amounts of
active ingredient, diluent and surfactant within the following
approximate ranges in the Formulation Table which add up to 100
percent by weight.
TABLE-US-00002 FORMULATION TABLE Weight Percent Active Ingredient
Diluent Surfactant Water-Dispersible and Water-soluble 0.001-90
0-99.999 0-15 Granules, Tablets and Powders. Oil Dispersions,
Suspensions, 1-50 40-99 0-50 Emulsions, Solutions (including
Emulsifiable Concentrates) Dusts 1-25 70-99 0-5 Granules and
Pellets 0.001-95 5-99.999 0-15 High Strength Compositions 90-99
0-10 0-2
[0103] Solid diluents include, for example, clays such as
bentonite, montmorillonite, attapulgite and kaolin, gypsum,
cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars
(e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth,
urea, calcium carbonate, sodium carbonate and bicarbonate, and
sodium sulfate. Typical solid diluents are described in Watkins et
al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed.,
Dorland Books, Caldwell, N.J.
[0104] Liquid diluents include, for example, water,
N,N-dimethylalkanamides (e.g., N,N-dimethylformamide), limonene,
dimethyl sulfoxide, N-alkylpyrrolidones (e.g.,
N-methylpyrrolidinone), ethylene glycol, triethylene glycol,
propylene glycol, dipropylene glycol, polypropylene glycol,
propylene carbonate, butylene carbonate, paraffins (e.g., white
mineral oils, normal paraffins, isoparaffins), alkylbenzenes,
alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol,
triacetin, aromatic hydrocarbons, dearomatized aliphatics,
alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone,
2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone,
acetates such as isoamyl acetate, hexyl acetate, heptyl acetate,
octyl acetate, nonyl acetate, acetate and isobornyl acetate, other
esters such as alkylated lactate esters, dibasic esters and
.gamma.-butyrolactone, and alcohols, which can be linear, branched,
saturated or unsaturated, such as methanol, ethanol, n-propanol,
isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol,
2-ethylhexanol, n-octanol, decanol, isodecyl alcohol,
isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol,
oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone
alcohol and benzyl alcohol. Liquid diluents also include glycerol
esters of saturated and unsaturated fatty acids (typically
C.sub.6-C.sub.22), such as plant seed and fruit oils (e.g., oils of
olive, castor, linseed, sesame, corn (maize), peanut, sunflower,
grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and
palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow,
lard, cod liver oil, fish oil), and mixtures thereof. Liquid
diluents also include alkylated fatty acids (e.g., methylated,
ethylated, butylated) wherein the fatty acids may be obtained by
hydrolysis of glycerol esters from plant and animal sources, and
can be purified by distillation. Typical liquid diluents are
described in Marsden, Solvents Guide, 2nd Ed., Interscience, New
York, 1950.
[0105] The solid and liquid compositions of the present invention
often include one or more surfactants. Surfactants can be
classified as nonionic, anionic or cationic. Nonionic surfactants
useful for the present compositions include, but are not limited
to: alcohol alkoxylates such as alcohol alkoxylates based on
natural and synthetic alcohols (which may be branched or linear)
and prepared from the alcohols and ethylene oxide, propylene oxide,
butylene oxide or mixtures thereof; amine ethoxylates,
alkanolamides and ethoxylated alkanolamides; alkoxylated
triglycerides such as ethoxylated soybean, castor and rapeseed
oils; alkylphenol alkoxylates such as octylphenol ethoxylates,
nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl
phenol ethoxylates (prepared from the phenols and ethylene oxide,
propylene oxide, butylene oxide or mixtures thereof); block
polymers prepared from ethylene oxide or propylene oxide and
reverse block polymers where the terminal blocks are prepared from
propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters
and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol
(including those prepared from ethylene oxide, propylene oxide,
butylene oxide or mixtures thereof); fatty acid esters, glycerol
esters, lanolin-based derivatives, polyethoxylate esters such as
polyethoxylated sorbitan fatty acid esters, polyethoxylated
sorbitol fatty acid esters and polyethoxylated glycerol fatty acid
esters; other sorbitan derivatives such as sorbitan esters;
polymeric surfactants such as random copolymers, block copolymers,
alkyd peg (polyethylene glycol) resins, graft or comb polymers and
star polymers; polyethylene glycols (pegs); polyethylene glycol
fatty acid esters; silicone-based surfactants; and
sugar-derivatives such as sucrose esters, alkyl polyglycosides and
alkyl polysaccharides.
[0106] Useful anionic surfactants include, but are not limited to:
alkylaryl sulfonic acids and their salts; carboxylated alcohol or
alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and
lignin derivatives such as lignosulfonates; maleic or succinic
acids or their anhydrides; olefin sulfonates; phosphate esters such
as phosphate esters of alcohol alkoxylates, phosphate esters of
alkylphenol alkoxylates and phosphate esters of styryl phenol
ethoxylates; protein-based surfactants; sarcosine derivatives;
styryl phenol ether sulfate; sulfates and sulfonates of oils and
fatty acids; sulfates and sulfonates of ethoxylated alkylphenols;
sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates
of amines and amides such as N,N-alkyltaurates; sulfonates of
benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes;
sulfonates of condensed naphthalenes; sulfonates of naphthalene and
alkyl naphthalene; sulfonates of fractionated petroleum;
sulfosuccinamates; and sulfosuccinates and their derivatives such
as dialkyl sulfosuccinate salts.
[0107] Useful cationic surfactants include, but are not limited to:
amides and ethoxylated amides; amines such as N-alkyl
propanediamines, tripropylenetriamines and dipropylenetetramines,
and ethoxylated amines, ethoxylated diamines and propoxylated
amines (prepared from the amines and ethylene oxide, propylene
oxide, butylene oxide or mixtures thereof); amine salts such as
amine acetates and diamine salts; quaternary ammonium salts such as
quaternary salts, ethoxylated quaternary salts and diquaternary
salts; and amine oxides such as alkyldimethylamine oxides and
bis-(2-hydroxyethyl)-alkylamine oxides.
[0108] Also useful for the present compositions are mixtures of
nonionic and anionic surfactants or mixtures of nonionic and
cationic surfactants. Nonionic, anionic and cationic surfactants
and their recommended uses are disclosed in a variety of published
references including McCutcheon's Emulsifiers and Detergents,
annual American and International Editions published by
McCutcheon's Division, The Manufacturing Confectioner Publishing
Co.; Sisely and Wood, Encyclopedia of Surface Active Agents,
Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B.
Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and
Sons, New York, 1987.
[0109] Compositions of this invention may also contain formulation
auxiliaries and additives, known to those skilled in the art as
formulation aids. Such formulation auxiliaries and additives may
control: pH (buffers), foaming during processing (antifoams such
polyorganosiloxanes (e.g., Rhodorsil.RTM. 416)), sedimentation of
active ingredients (suspending agents), viscosity (thixotropic
thickeners), in-container microbial growth (antimicrobials),
product freezing (antifreezes), color (dyes/pigment dispersions
(e.g., Pro-Ized.RTM. Colorant Red)), wash-off (film formers or
stickers), evaporation (evaporation retardants), and other
formulation attributes. Film formers include, for example,
polyvinyl acetates, polyvinyl acetate copolymers,
polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols,
polyvinyl alcohol copolymers and waxes. Examples of formulation
auxiliaries and additives include those listed in McCutcheon's
Volume 2: Functional Materials, annual International and North
American editions published by McCutcheon's Division, The
Manufacturing Confectioner Publishing Co.; and PCT Publication WO
03/024222.
[0110] Solutions, including emulsifiable concentrates, can be
prepared by simply mixing the ingredients. If the solvent of a
liquid composition intended for use as an emulsifiable concentrate
is water-immiscible, an emulsifier is typically added to emulsify
the active-containing solvent upon dilution with water. Active
ingredient slurries, with particle diameters of up to 2,000 .mu.m
can be wet milled using media mills to obtain particles with
average diameters below 3 .mu.m. Aqueous slurries can be made into
finished suspension concentrates (see, for example, U.S. Pat. No.
3,060,084) or further processed by spray drying to form
water-dispersible granules. Dry formulations usually require dry
milling processes, which produce average particle diameters in the
2 to 10 .mu.m range. Dusts and powders can be prepared by blending
and, usually, grinding as in a hammer mill or fluid-energy mill.
Granules and pellets can be prepared by spraying the active
material upon preformed granular carriers or by agglomeration
techniques. See Browning, "Agglomeration", Chemical Engineering,
Dec. 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th
Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO
91/13546. Pellets can be prepared as described in U.S. Pat. No.
4,172,714. Water-dispersible and water-soluble granules can be
prepared as taught in U.S. Pat. No. 4,144,050, U.S. Pat. No.
3,920,442 and DE 3,246,493. Tablets can be prepared as taught in
U.S. Pat. No. 5,180,587, U.S. Pat. No. 5,232,701 and U.S. Pat. No.
5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S.
Pat. No. 3,299,566.
[0111] For further information regarding the art of formulation,
see T. S. Woods, "The Formulator's Toolbox--Product Forms for
Modern Agriculture" in Pesticide Chemistry and Bioscience, The
Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds.,
Proceedings of the 9th International Congress on Pesticide
Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp.
120-133. See also U.S. Pat. No. 3,235,361, Col. 6, line 16 through
Col. 7, line 19 and Examples 10-41; U.S. Pat. No. 3,309,192, Col.
5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41,
52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. Pat.
No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples
1-4; Klingman, Weed Control as a Science, John Wiley and Sons,
Inc., New York, 1961, pp 81-96; Hance et al., Weed Control
Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989;
and Developments in formulation technology, PJB Publications,
Richmond, UK, 2000.
[0112] In the following Examples, all percentages are by weight and
all formulations are prepared in conventional ways. Compound
numbers refer to compounds in Index Table A.
Example A
TABLE-US-00003 [0113] High Strength Concentrate Compound 1 98.5%
silica aerogel 0.5% synthetic amorphous fine silica 1.0%
Example B
TABLE-US-00004 [0114] Wettable Powder Compound 2 65.0%
dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate
4.0% sodium silicoaluminate 6.0% montmorillonite (calcined)
23.0%
Example C
TABLE-US-00005 [0115] Granule Compound 3 10.0% attapulgite granules
(low volatile matter, 90.0% 0.71/0.30 mm; U.S.S. No. 25-50
sieves)
Example D
TABLE-US-00006 [0116] Aqueous Suspension Compound 4 25.0% hydrated
attapulgite 3.0% crude calcium ligninsulfonate 10.0% sodium
dihydrogen phosphate 0.5% water 61.5.0%
Example E
TABLE-US-00007 [0117] Extruded Pellet Compound 5 25.0% anhydrous
sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium
alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite
59.0%
Example F
TABLE-US-00008 [0118] Microemulsion Compound 1 5.0%
polyvinylpyrrolidone-vinyl acetate copolymer 30.0% C.sub.8-C.sub.10
alkylpolyglycoside 30.0% glyceryl monooleate 15.0% Water 20.0%
Example G
TABLE-US-00009 [0119] Emulsifiable Concentrate Compound 2 10.0%
polyoxyethylene sorbitol hexoleate 20.0% C.sub.6-C.sub.10 fatty
acid methyl ester 70.0%
[0120] Formulations such as those in the Formulation Table above
are typically diluted with water to form aqueous compositions
suitable for convenient application. Aqueous compositions for
direct applications to the plant or portion thereof (e.g., spray
tank compositions) typically at least about 1 ppm or more (e.g.,
from 1 ppm to 300 ppm) of the compound(s) of this invention.
[0121] The compounds of this invention are useful as plant disease
control agents. The present invention therefore further comprises a
method for controlling plant diseases caused by fungal plant
pathogens comprising applying to the plant or portion thereof to be
protected, or to the plant seed to be protected, an effective
amount of a compound of the invention or a fungicidal composition
containing said compound. The compounds and/or compositions of this
invention provide control of diseases caused by a broad spectrum of
fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete
and Deuteromycete classes. They are effective in controlling a
broad spectrum of plant diseases, particularly foliar pathogens of
ornamental, turf, vegetable, field, cereal, and fruit crops. These
pathogens include: Oomycetes, including Phytophthora diseases such
as Phytophthora infestans, Phytophthora megasperma, Phytophthora
parasitica, Phytophthora cinnamomi and Phytophthora capsici,
Pythium diseases such as Pythium aphanidermatum, and diseases in
the Peronosporaceae family such as Plasmopara viticola, Peronospora
spp. (including Peronospora tabacina and Peronospora parasitica),
Pseudoperonospora spp. (including Pseudoperonospora cubensis) and
Bremia lactucae; Ascomycetes, including Alternaria diseases such as
Alternaria solani and Alternaria brassicae, Guignardia diseases
such as Guignardia bidwell, Venturia diseases such as Venturia
inaequalis, Septoria diseases such as Septoria nodorum and Septoria
tritici, powdery mildew diseases such as Erysiphe spp. (including
Erysiphe graminis and Erysiphe polygoni), Uncinula necatur,
Sphaerotheca fuligena and Podosphaera leucotricha,
Pseudocercosporella herpotrichoides, Botrytis diseases such as
Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such
as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis
viticola, Helminthosporium diseases such as Helminthosporium
tritici repentis, Pyrenophora teres, anthracnose diseases such as
Glomerella or Colletotrichum spp. (such as Colletotrichum
graminicola and Colletotrichum orbiculare), and Gaeumannomyces
graminis; Basidiomycetes, including rust diseases caused by
Puccinia spp. (such as Puccinia recondite, Puccinia striiformis,
Puccinia hordei, Puccinia graminis and Puccinia arachidis),
Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens
including Rhizoctonia spp. (such as Rhizoctonia solani); Fusarium
diseases such as Fusarium roseum, Fusarium graminearum and Fusarium
oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium
secalis; Cercosporidium personatum, Cercospora arachidicola and
Cercospora beticola; and other genera and species closely related
to these pathogens. In addition to their fungicidal activity, the
compositions or combinations also have activity against bacteria
such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas
syringae, and other related species.
[0122] Plant disease control is ordinarily accomplished by applying
an effective amount of a compound of this invention either pre- or
post-infection, to the portion of the plant to be protected such as
the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the
media (soil or sand) in which the plants to be protected are
growing. The compounds can also be applied to seeds to protect the
seeds and seedlings developing from the seeds. The compounds can
also be applied through irrigation water to treat plants.
[0123] Rates of application for these compounds can be influenced
by many factors of the environment and should be determined under
actual use conditions. Foliage can normally be protected when
treated at a rate of from less than about 1 g/ha to about 5,000
g/ha of active ingredient. Seed and seedlings can normally be
protected when seed is treated at a rate of from about 0.1 to about
10 g per kilogram of seed.
[0124] Compounds of this invention can also be mixed with one or
more other biologically active compounds or agents including
fungicides, insecticides, nematocides, bactericides, acaricides,
herbicides, herbicide safeners, growth regulators such as insect
molting inhibitors and rooting stimulants, chemosterilants,
semiochemicals, repellents, attractants, pheromones, feeding
stimulants, plant nutrients, other biologically active compounds or
entomopathogenic bacteria, virus or fungi to form a multi-component
pesticide giving an even broader spectrum of agricultural
protection. Thus the present invention also pertains to a
composition comprising a fungicidally effective amount of a
compound of Formula 1 and a biologically effective amount of at
least one additional biologically active compound or agent and can
further comprise at least one of a surfactant, a solid diluent or a
liquid diluent. The other biologically active compounds or agents
can be formulated in compositions comprising at least one of a
surfactant, solid or liquid diluent. For mixtures of the present
invention, one or more other biologically active compounds or
agents can be formulated together with a compound of Formula 1, to
form a premix, or one or more other biologically active compounds
or agents can be formulated separately from the compound of Formula
1, and the formulations combined together before application (e.g.,
in a spray tank) or, alternatively, applied in succession.
[0125] Of note is a composition which in addition to the compound
of Formula 1 include at least one fungicidal compound selected from
the group consisting of the classes (1) methyl benzimidazole
carbamate (MBC) fungicides; (2) dicarboximide fungicides; (3)
demethylation inhibitor (DMI) fungicides; (4) phenylamide
fungicides; (5) amine/morpholine fungicides; (6) phospholipid
biosynthesis inhibitor fungicides; (7) carboxamide fungicides; (8)
hydroxy(2-amino-)pyrimidine fungicides; (9) anilinopyrimidine
fungicides; (10) N-phenyl carbamate fungicides; (11) quinone
outside inhibitor (QoI) fungicides; (12) phenylpyrrole fungicides;
(13) quinoline fungicides; (14) lipid peroxidation inhibitor
fungicides; (15) melanin biosynthesis inhibitors-reductase (MBI-R)
fungicides; (16) melanin biosynthesis inhibitors-dehydratase
(MBI-D) fungicides; (17) hydroxyanilide fungicides; (18)
squalene-epoxidase inhibitor fungicides; (19) polyoxin fungicides;
(20) phenylurea fungicides; (21) quinone inside inhibitor (QiI)
fungicides; (22) benzamide fungicides; (23) enopyranuronic acid
antibiotic fungicides; (24) hexopyranosyl antibiotic fungicides;
(25) glucopyranosyl antibiotic: protein synthesis fungicides; (26)
glucopyranosyl antibiotic: trehalase and inositol biosynthesis
fungicides; (27) cyanoacetamideoxime fungicides; (28) carbamate
fungicides; (29) oxidative phosphorylation uncoupling fungicides;
(30) organo tin fungicides; (31) carboxylic acid fungicides; (32)
heteroaromatic fungicides; (33) phosphonate fungicides; (34)
phthalamic acid fungicides; (35) benzotriazine fungicides; (36)
benzene-sulfonamide fungicides; (37) pyridazinone fungicides; (38)
thiophene-carboxamide fungicides; (39) pyrimidinamide fungicides;
(40) carboxylic acid amide (CAA) fungicides; (41) tetracycline
antibiotic fungicides; (42) thiocarbamate fungicides; (43)
benzamide fungicides; (44) host plant defense induction fungicides;
(45) multi-site contact activity fungicides; (46) fungicides other
than classes (1) through (45); and salts of compounds of classes
(1) through (46).
[0126] Further descriptions of these classes of fungicidal
compounds are provided below.
[0127] (1) "Methyl benzimidazole carbamate (MBC) fungicides"
(Fungicide Resistance Action Committee (FRAC) code 1) inhibit
mitosis by binding to .beta.-tubulin during microtubule assembly.
Inhibition of microtubule assembly can disrupt cell division,
transport within the cell and cell structure. Methyl benzimidazole
carbamate fungicides include benzimidazole and thiophanate
fungicides. The benzimidazoles include benomyl, carbendazim,
fuberidazole and thiabendazole. The thiophanates include
thiophanate and thiophanate-methyl.
[0128] (2) "Dicarboximide fungicides" (Fungicide Resistance Action
Committee (FRAC) code 2) are proposed to inhibit a lipid
peroxidation in fungi through interference with NADH cytochrome c
reductase. Examples include chlozolinate, iprodione, procymidone
and vinclozolin.
[0129] (3) "Demethylation inhibitor (DMI) fungicides" (Fungicide
Resistance Action Committee (FRAC) code 3) inhibit Cl4-demethylase,
which plays a role in sterol production. Sterols, such as
ergosterol, are needed for membrane structure and function, making
them essential for the development of functional cell walls.
Therefore, exposure to these fungicides results in abnormal growth
and eventually death of sensitive fungi. DMI fungicides are divided
between several chemical classes: azoles (including triazoles and
imidazoles), pyrimidines, piperazines and pyridines. The triazoles
include azaconazole, bitertanol, bromuconazole, cyproconazole,
difenoconazole, diniconazole (including diniconazole-M),
epoxiconazole, fenbuconazole, fluquinconazole, flusilazole,
flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole,
myclobutanil, penconazole, propiconazole, prothioconazole,
simeconazole, tebuconazole, tetraconazole, triadimefon,
triadimenol, triticonazole and uniconazole. The imidazoles include
clotrimazole, imazalil, oxpoconazole, prochloraz, pefurazoate and
triflumizole. The pyrimidines include fenarimol and nuarimol. The
piperazines include triforine. The pyridines include pyrifenox.
Biochemical investigations have shown that all of the above
mentioned fungicides are DMI fungicides as described by K. H. Kuck
et al. in Modern Selective Fungicides--Properties, Applications and
Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New
York, 1995, 205-258.
[0130] (4) "Phenylamide fungicides" (Fungicide Resistance Action
Committee (FRAC) code 4) are specific inhibitors of RNA polymerase
in Oomycete fungi. Sensitive fungi exposed to these fungicides show
a reduced capacity to incorporate uridine into rRNA. Growth and
development in sensitive fungi is prevented by exposure to this
class of fungicide. Phenylamide fungicides include acylalanine,
oxazolidinone and butyrolactone fungicides. The acylalanines
include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl and
metalaxyl-M/mefenoxam. The oxazolidinones include oxadixyl. The
butyrolactones include ofurace.
[0131] (5) "Amine/morpholine fungicides" (Fungicide Resistance
Action Committee (FRAC) code 5) inhibit two target sites within the
sterol biosynthetic pathway, .DELTA..sup.8.fwdarw..DELTA..sup.7
isomerase and .DELTA..sup.14 reductase. Sterols, such as
ergosterol, are needed for membrane structure and function, making
them essential for the development of functional cell walls.
Therefore, exposure to these fungicides results in abnormal growth
and eventually death of sensitive fungi. Amine/morpholine
fungicides (also known as non-DMI sterol biosynthesis inhibitors)
include morpholine, piperidine and spiroketal-amine fungicides. The
morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph
and trimorphamide. The piperidines include fenpropidin and
piperalin. The spiroketal-amines include spiroxamine.
[0132] (6) "Phospholipid biosynthesis inhibitor fungicides"
(Fungicide Resistance Action Committee (FRAC) code 6) inhibit
growth of fungi by affecting phospholipid biosynthesis.
Phospholipid biosynthesis fungicides include phosphorothiolate and
dithiolane fungicides. The phosphorothiolates include edifenphos,
iprobenfos and pyrazophos. The dithiolanes include
isoprothiolane.
[0133] (7) "Carboxamide fungicides" (Fungicide Resistance Action
Committee (FRAC) code 7) inhibit Complex II (succinate
dehydrogenase) fungal respiration by disrupting a key enzyme in the
Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting
respiration prevents the fungus from making ATP, and thus inhibits
growth and reproduction. Carboxamide fungicides include benzamides,
furan carboxamides, oxathiin carboxamides, thiazole carboxamides,
pyrazole carboxamides and pyridine carboxamides. The benzamides
include benodanil, flutolanil and mepronil. The furan carboxamides
include fenfuram. The oxathiin carboxamides include carboxin and
oxycarboxin. The thiazole carboxamides include thifluzamide. The
pyrazole carboxamides include furametpyr, penthiopyrad, bixafen,
N-[2-(1S,2R)-[1,1'-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-
-1H-pyrazole-4-carboxamide and
N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbo-
xamide. The pyridine carboxamides include boscalid.
[0134] (8) "Hydroxy(2-amino-)pyrimidine fungicides" (Fungicide
Resistance Action Committee (FRAC) code 8) inhibit nucleic acid
synthesis by interfering with adenosine deaminase. Examples include
bupirimate, dimethirimol and ethirimol.
[0135] (9) "Anilinopyrimidine fungicides" (Fungicide Resistance
Action Committee (FRAC) code 9) are proposed to inhibit
biosynthesis of the amino acid methionine and to disrupt the
secretion of hydrolytic enzymes that lyse plant cells during
infection. Examples include cyprodinil, mepanipyrim and
pyrimethanil.
[0136] (10) "N-Phenyl carbamate fungicides" (Fungicide Resistance
Action Committee (FRAC) code 10) inhibit mitosis by binding to
.beta.-tubulin and disrupting microtubule assembly. Inhibition of
microtubule assembly can disrupt cell division, transport within
the cell and cell structure. Examples include diethofencarb.
[0137] (11) "Quinone outside inhibitor (QoI) fungicides" (Fungicide
Resistance Action Committee (FRAC) code 11) inhibit Complex III
mitochondrial respiration in fungi by affecting ubiquinol oxidase.
Oxidation of ubiquinol is blocked at the "quinone outside"
(Q.sub.o) site of the cytochrome bc.sub.1 complex, which is located
in the inner mitochondrial membrane of fungi. Inhibiting
mitochondrial respiration prevents normal fungal growth and
development. Quinone outside inhibitor fungicides (also known as
strobilurin fungicides) include methoxyacrylate, methoxycarbamate,
oximinoacetate, oximinoacetamide, oxazolidinedione,
dihydrodioxazine, imidazolinone and benzylcarbamate fungicides. The
methoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) and
picoxystrobin. The methoxycarbamates include pyraclostrobin. The
oximinoacetates include kresoxim-methyl and trifloxystrobin. The
oximinoacetamides include dimoxystrobin, metominostrobin,
orysastrobin,
.alpha.-[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]ethoxy]-
imino]-methyl]benzeneacetamide and
2-[[[3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-ylidene]-amino]oxy]methyl-
]-.alpha.-(methoxyimino)-N-methylbenzeneacetamide. The
oxazolidinediones include famoxadone. The dihydrodioxazines include
fluoxastrobin. The imidazolinones include fenamidone. The
benzylcarbamates include pyribencarb.
[0138] (12) "Phenylpyrrole fungicides" (Fungicide Resistance Action
Committee (FRAC) code 12) inhibit a MAP protein kinase associated
with osmotic signal transduction in fungi. Fenpiclonil and
fludioxonil are examples of this fungicide class.
[0139] (13) "Quinoline fungicides" (Fungicide Resistance Action
Committee (FRAC) code 13) are proposed to inhibit signal
transduction by affecting G-proteins in early cell signaling. They
have been shown to interfere with germination and/or appressorium
formation in fungi that cause powder mildew diseases. Quinoxyfen is
an example of this class of fungicide.
[0140] (14) "Lipid peroxidation inhibitor fungicides" (Fungicide
Resistance Action Committee (FRAC) code 14) are proposed to inhibit
lipid peroxidation which affects membrane synthesis in fungi.
Members of this class, such as etridiazole, may also affect other
biological processes such as respiration and melanin biosynthesis.
Lipid peroxidation fungicides include aromatic carbon and
1,2,4-thiadiazole fungicides. The aromatic carbon fungicides
include biphenyl, chloroneb, dicloran, quintozene, tecnazene and
tolclofos-methyl. The 1,2,4-thiadiazole fungicides include
etridiazole.
[0141] (15) "Melanin biosynthesis inhibitors-reductase (MBI-R)
fungicides" (Fungicide Resistance Action Committee (FRAC) code
16.1) inhibit the naphthal reduction step in melanin biosynthesis.
Melanin is required for host plant infection by some fungi. Melanin
biosynthesis inhibitors-reductase fungicides include
isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole
fungicides. The isobenzofuranones include fthalide. The
pyrroloquinolinones include pyroquilon. The triazolobenzothiazoles
include tricyclazole.
[0142] (16) "Melanin biosynthesis inhibitors-dehydratase (MBI-D)
fungicides" (Fungicide Resistance Action Committee (FRAC) code
16.2) inhibit scytalone dehydratase in melanin biosynthesis.
Melanin in required for host plant infection by some fungi. Melanin
biosynthesis inhibitors-dehydratase fungicides include
cyclopropanecarboxamide, carboxamide and propionamide fungicides.
The cyclopropanecarboxamides include carpropamid. The carboxamides
include diclocymet. The propionamides include fenoxanil.
[0143] (17) "Hydroxyanilide fungicides (Fungicide Resistance Action
Committee (FRAC) code 17) inhibit C4-demethylase which plays a role
in sterol production. Examples include fenhexamid.
[0144] (18) "Squalene-epoxidase inhibitor fungicides" (Fungicide
Resistance Action Committee (FRAC) code 18) inhibit
squalene-epoxidase in ergosterol biosynthesis pathway. Sterols such
as ergosterol are needed for membrane structure and function,
making them essential for the development of functional cell walls.
Therefore exposure to these fungicides results in abnormal growth
and eventually death of sensitive fungi. Squalene-epoxidase
inhibitor fungicides include thiocarbamate and allylamine
fungicides. The thiocarbamates include pyributicarb. The
allylamines include naftifine and terbinafine.
[0145] (19) "Polyoxin fungicides" (Fungicide Resistance Action
Committee (FRAC) code 19) inhibit chitin synthase. Examples include
polyoxin.
[0146] (20) "Phenylurea fungicides" (Fungicide Resistance Action
Committee (FRAC) code
[0147] 20) are proposed to affect cell division. Examples include
pencycuron.
[0148] (21) "Quinone inside inhibitor (QiI) fungicides" (Fungicide
Resistance Action Committee (FRAC) code 21) inhibit Complex III
mitochondrial respiration in fungi by affecting ubiquinol
reductase. Reduction of ubiquinol is blocked at the "quinone
inside" (Q.sub.i) site of the cytochrome bc.sub.1 complex, which is
located in the inner mitochondrial membrane of fungi. Inhibiting
mitochondrial respiration prevents normal fungal growth and
development. Quinone inside inhibitor fungicides include
cyanoimidazole and sulfamoyltriazole fungicides. The
cyanoimidazoles include cyazofamid. The sulfamoyltriazoles include
amisulbrom.
[0149] (22) "Benzamide fungicides" (Fungicide Resistance Action
Committee (FRAC) code 22) inhibit mitosis by binding to
.beta.-tubulin and disrupting microtubule assembly Inhibition of
microtubule assembly can disrupt cell division, transport within
the cell and cell structure. Examples include zoxamide.
[0150] (23) "Enopyranuronic acid antibiotic fungicides" (Fungicide
Resistance Action Committee (FRAC) code 23) inhibit growth of fungi
by affecting protein biosynthesis. Examples include
blasticidin-S.
[0151] (24) "Hexopyranosyl antibiotic fungicides" (Fungicide
Resistance Action Committee (FRAC) code 24) inhibit growth of fungi
by affecting protein biosynthesis. Examples include
kasugamycin.
[0152] (25) "Glucopyranosyl antibiotic: protein synthesis
fungicides" (Fungicide Resistance Action Committee (FRAC) code 25)
inhibit growth of fungi by affecting protein biosynthesis. Examples
include streptomycin.
[0153] (26) "Glucopyranosyl antibiotic: trehalase and inositol
biosynthesis fungicides" (Fungicide Resistance Action Committee
(FRAC) code 26) inhibit trehalase in inositol biosynthesis pathway.
Examples include validamycin.
[0154] (27) "Cyanoacetamideoxime fungicides (Fungicide Resistance
Action Committee (FRAC) code 27) include cymoxanil.
[0155] (28) "Carbamate fungicides" (Fungicide Resistance Action
Committee (FRAC) code 28) are considered multi-site inhibitors of
fungal growth. They are proposed to interfere with the synthesis of
fatty acids in cell membranes, which then disrupts cell membrane
permeability. Propamacarb, propamacarb-hydrochloride, iodocarb, and
prothiocarb are examples of this fungicide class.
[0156] (29) "Oxidative phosphorylation uncoupling fungicides"
(Fungicide Resistance Action Committee (FRAC) code 29) inhibit
fungal respiration by uncoupling oxidative phosphorylation.
Inhibiting respiration prevents normal fungal growth and
development. This class includes 2,6-dinitroanilines such as
fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl
crotonates such as dinocap, meptyldinocap and binapacryl.
[0157] (30) "Organo tin fungicides" (Fungicide Resistance Action
Committee (FRAC) code 30) inhibit adenosine triphosphate (ATP)
synthase in oxidative phosphorylation pathway. Examples include
fentin acetate, fentin chloride and fentin hydroxide.
[0158] (31) "Carboxylic acid fungicides" (Fungicide Resistance
Action Committee (FRAC) code 31) inhibit growth of fungi by
affecting deoxyribonucleic acid (DNA) topoisomerase type II
(gyrase). Examples include oxolinic acid.
[0159] (32) "Heteroaromatic fungicides" (Fungicide Resistance
Action Committee (FRAC) code 32) are proposed to affect
DNA/ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides
include isoxazole and isothiazolone fungicides. The isoxazoles
include hymexazole and the isothiazolones include octhilinone.
[0160] (33) "Phosphonate fungicides" (Fungicide Resistance Action
Committee (FRAC) code 33) include phosphorus acid and its various
salts, including fosetyl-aluminum.
[0161] (34) "Phthalamic acid fungicides" (Fungicide Resistance
Action Committee (FRAC) code 34) include teclofthalam.
[0162] (35) "Benzotriazine fungicides" (Fungicide Resistance Action
Committee (FRAC) code 35) include triazoxide.
[0163] (36) "Benzene-sulfonamide fungicides" (Fungicide Resistance
Action Committee (FRAC) code 36) include flusulfamide.
[0164] (37) "Pyridazinone fungicides" (Fungicide Resistance Action
Committee (FRAC) code 37) include diclomezine.
[0165] (38) "Thiophene-carboxamide fungicides" (Fungicide
Resistance Action Committee (FRAC) code 38) are proposed to affect
ATP production. Examples include silthiofam.
[0166] (39) "Pyrimidinamide fungicides" (Fungicide Resistance
Action Committee (FRAC) code 39) inhibit growth of fungi by
affecting phospholipid biosynthesis and include diflumetorim.
[0167] (40) "Carboxylic acid amide (CAA) fungicides" (Fungicide
Resistance Action Committee (FRAC) code 40) are proposed to inhibit
phospholipid biosynthesis and cell wall deposition. Inhibition of
these processes prevents growth and leads to death of the target
fungus. Carboxylic acid amide fungicides include cinnamic acid
amide, valinamide carbamate and mandelic acid amide fungicides. The
cinnamic acid amides include dimethomorph and flumorph. The
valinamide carbamates include benthiavalicarb,
benthiavalicarb-isopropyl, iprovalicarb and valiphenal. The
mandelic acid amides include mandipropamid,
N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3--
methyl-2-[(methylsulfonyl)amino]butanamide and
N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3--
methyl-2-[(ethylsulfonyl)amino]butanamide.
[0168] (41) "Tetracycline antibiotic fungicides" (Fungicide
Resistance Action Committee (FRAC) code 41) inhibit growth of fungi
by affecting complex 1 nicotinamide adenine dinucleotide (NADH)
oxidoreductase. Examples include oxytetracycline.
[0169] (42) "Thiocarbamate fungicides (b42)" (Fungicide Resistance
Action Committee (FRAC) code 42) include methasulfocarb.
[0170] (43) "Benzamide fungicides" (Fungicide Resistance Action
Committee (FRAC) code 43) inhibit growth of fungi by delocalization
of spectrin-like proteins. Examples include acylpicolide fungicides
such as fluopicolide and fluopyram.
[0171] (44) "Host plant defense induction fungicides" (Fungicide
Resistance Action Committee (FRAC) code P) induce host plant
defense mechanisms. Host plant defense induction fungicides include
benzo-thiadiazole, benzisothiazole and thiadiazole-carboxamide
fungicides. The benzo-thiadiazoles include acibenzolar-5-methyl.
The benzisothiazoles include probenazole. The
thiadiazole-carboxamides include tiadinil and isotianil.
[0172] (45) "Multi-site contact fungicides" inhibit fungal growth
through multiple sites of action and have contact/preventive
activity. This class of fungicides includes: (45.1) "copper
fungicides" (Fungicide Resistance Action Committee (FRAC) code
M1)", (45.2) "sulfur fungicides" (Fungicide Resistance Action
Committee (FRAC) code M2), (45.3) "dithiocarbamate fungicides"
(Fungicide Resistance Action Committee (FRAC) code M3), (45.4)
"phthalimide fungicides" (Fungicide Resistance Action Committee
(FRAC) code M4), (45.5) "chloronitrile fungicides" (Fungicide
Resistance Action Committee (FRAC) code M5), (45.6) "sulfamide
fungicides" (Fungicide Resistance Action Committee (FRAC) code M6),
(45.7) "guanidine fungicides" (Fungicide Resistance Action
Committee (FRAC) code M7), (45.8) "triazine fungicides" (Fungicide
Resistance Action Committee (FRAC) code M8) and (45.9) "quinone
fungicides" (Fungicide Resistance Action Committee (FRAC) code M9).
"Copper fungicides" are inorganic compounds containing copper,
typically in the copper(II) oxidation state; examples include
copper oxychloride, copper sulfate and copper hydroxide, including
compositions such as Bordeaux mixture (tribasic copper sulfate).
"Sulfur fungicides" are inorganic chemicals containing rings or
chains of sulfur atoms; examples include elemental sulfur.
"Dithiocarbamate fungicides" contain a dithiocarbamate molecular
moiety; examples include mancozeb, metiram, propineb, ferbam,
maneb, thiram, zineb and ziram. "Phthalimide fungicides" contain a
phthalimide molecular moiety; examples include folpet, captan and
captafol. "Chloronitrile fungicides" contain an aromatic ring
substituted with chloro and cyano; examples include chlorothalonil.
"Sulfamide fungicides" include dichlofluanid and tolyfluanid.
"Guanidine fungicides" include dodine, guazatine, iminoctadine
albesilate and iminoctadine triacetate. "Triazine fungicides"
include anilazine. "Quinone fungicides" include dithianon.
[0173] (46) "Fungicides other than fungicides of classes (1)
through (45)" include certain fungicides whose mode of action may
be unknown. These include: (46.1) "thiazole carboxamide fungicides"
(Fungicide Resistance Action Committee (FRAC) code U5), (46.2)
"phenyl-acetamide fungicides" (Fungicide Resistance Action
Committee (FRAC) code U6), (46.3) "quinazolinone fungicides"
(Fungicide Resistance Action Committee (FRAC) code U7) and (46.4)
"benzophenone fungicides" (Fungicide Resistance Action Committee
(FRAC) code U8). The thiazole carboxamides include ethaboxam. The
phenyl-acetamides include cyflufenamid and
N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]-me-
thyleneThenzeneacetamide. The quinazolinones include proquinazid
and 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one. The
benzophenones include metrafenone. The (b46) class also includes
bethoxazin, neo-asozin (ferric methanearsonate), pyrrolnitrin,
quinomethionate,
N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3--
methyl-2-[(methylsulfonyl)amino]butanamide,
N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3--
methyl-2-[(ethylsulfonyl)amino]-butanamide,
2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thi-
azo-lidinylidene]acetonitrile,
3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine,
4-fluorophenyl
N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate,
5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-yl)
[1,2,4]triazolo[1,5-a]pyrimidine,
N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide,
N-[[(cyclopropylmethoxy)-amino][6-(difluoromethoxy)-2,3-difluorophenyl]me-
thylene]benzeneacetamide,
N'-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-
-methylmethanimidamide and 1-[(2-propenylthio)
carbonyl]-2-(1-methylethyl)-4-(2-methylphenyl)-5-amino-1H-pyrazol-3-one.
[0174] Therefore of note is a mixture (i.e. composition) comprising
a compound of Formula 1 and at least one fungicidal compound
selected from the group consisting of the aforedescribed classes
(1) through (46). Also of note is a composition comprising said
mixture (in fungicidally effective amount) and further comprising
at least one additional component selected from the group
consisting of surfactants, solid diluents and liquid diluents. Of
particular note is a mixture (i.e. composition) comprising a
compound of Formula 1 and at least one fungicidal compound selected
from the group of specific compounds listed above in connection
with classes (1) through (46). Also of particular note is a
composition comprising said mixture (in fungicidally effective
amount) and further comprising at least one additional surfactant
selected from the group consisting of surfactants, solid diluents
and liquid diluents.
[0175] Examples of other biologically active compounds or agents
with which compounds of this invention can be formulated are:
insecticides such as abamectin, acephate, acetamiprid, amidoflumet
(S-1955), avermectin, azadirachtin, azinphos-methyl, bifenthrin,
bifenazate,
3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carb-
onyl]phenyl]-1H-pyrazole-5-carboxamide, buprofezin, carbofuran,
cartap, chlorantraniliprole (DPX-E2Y45), chlorfenapyr,
chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide,
clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin,
cyhalothrin, lambda-cyhalothrin, cypermethrin, cyromazine,
deltamethrin, diafenthiuron, diazinon, dieldrin, diflubenzuron,
dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin,
endosulfan, esfenvalerate, ethiprole, fenothiocarb, fenoxycarb,
fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide,
flucythrinate, tau-fluvalinate, flufenerim (UR-50701),
flufenoxuron, fonophos, halofenozide, hexaflumuron, hydramethylnon,
imidacloprid, indoxacarb, isofenphos, lufenuron, malathion,
metaflumizone, metaldehyde, methamidophos, methidathion, methomyl,
methoprene, methoxychlor, metofluthrin, monocrotophos,
methoxyfenozide, nitenpyram, nithiazine, novaluron, noviflumuron
(XDE-007), oxamyl, parathion, parathion-methyl, permethrin,
phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos,
profluthrin, pymetrozine, pyrafluprole, pyrethrin, pyridalyl,
pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine,
spinetoram, spinosad, spirodiclofen, spiromesifen (BSN 2060),
spirotetramat, sulprofos, tebufenozide, teflubenzuron, tefluthrin,
terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb,
thiosultap-sodium, tralomethrin, triazamate, trichlorfon and
triflumuron; and biological agents including entomopathogenic
bacteria, such as Bacillus thuringiensis subsp. aizawai, Bacillus
thuringiensis subsp. kurstaki, and the encapsulated
delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV,
MPVII); entomopathogenic fungi, such as green muscardine fungus;
and entomopathogenic virus including baculovirus, nucleopolyhedro
virus (NPV) such as HzNPV, AfNPV; and granulosis virus (GV) such as
CpGV.
[0176] Compounds of this invention and compositions thereof can be
applied to plants genetically transformed to express proteins toxic
to invertebrate pests (such as Bacillus thuringiensis
delta-endotoxins). The effect of the exogenously applied fungicidal
compounds of this invention may be synergistic with the expressed
toxin proteins.
[0177] General references for agricultural protectants (i.e.
insecticides, fungicides, nematocides, acaricides, herbicides and
biological agents) include The Pesticide Manual, 13th Edition, C.
D. S. Tomlin, Ed., British Crop Protection Council, Farnham,
Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. G.
Copping, Ed., British Crop Protection Council, Farnham, Surrey,
U.K., 2001.
[0178] For embodiments where one or more of these various mixing
partners are used, the weight ratio of these various mixing
partners (in total) to the compound of Formula 1 is typically
between about 1:3000 and about 3000:1. Of note are weight ratios
between about 1:300 and about 300:1 (for example ratios between
about 1:30 and about 30:1). One skilled in the art can easily
determine through simple experimentation the biologically effective
amounts of active ingredients necessary for the desired spectrum of
biological activity. It will be evident that including these
additional components may expand the spectrum of diseases
controlled beyond the spectrum controlled by the compound of
Formula 1 alone.
[0179] In certain instances, combinations of a compound of this
invention with other biologically active (particularly fungicidal)
compounds or agents (i.e. active ingredients) can result in a
greater-than-additive (i.e. synergistic) effect. Reducing the
quantity of active ingredients released in the environment while
ensuring effective pest control is always desirable. When synergism
of fungicidal active ingredients occurs at application rates giving
agronomically satisfactory levels of fungal control, such
combinations can be advantageous for reducing crop production cost
and decreasing environmental load.
[0180] Of note is a combination of a compound of Formula 1 with at
least one other fungicidal active ingredient. Of particular note is
such a combination where the other fungicidal active ingredient has
different site of action from the compound of Formula 1. In certain
instances, a combination with at least one other fungicidal active
ingredient having a similar spectrum of control but a different
site of action will be particularly advantageous for resistance
management. Thus, a composition of the present invention can
further comprise a biologically effective amount of at least one
additional fungicidal active ingredient having a similar spectrum
of control but a different site of action.
[0181] Of particular note are compositions which in addition to
compound of Formula 1 include at least one compound selected from
the group consisting of (1) alkylenebis(dithiocarbamate)
fungicides; (2) cymoxanil; (3) phenylamide fungicides; (4)
pyrimidinone fungicides; (5) chlorothalonil; (6) carboxamides
acting at complex II of the fungal mitochondrial respiratory
electron transfer site; (7) quinoxyfen; (8) metrafenone; (9)
cyflufenamid; (10) cyprodinil; (11) copper compounds; (12)
phthalimide fungicides; (13) fosetyl-aluminum; (14) benzimidazole
fungicides; (15) cyazofamid; (16) fluazinam; (17) iprovalicarb;
(18) propamocarb; (19) validomycin; (20) dichlorophenyl
dicarboximide fungicides; (21) zoxamide; (22) fluopicolide; (23)
mandipropamid; (24) carboxylic acid amides acting on phospholipid
biosynthesis and cell wall deposition; (25) dimethomorph; (26)
non-DMI sterol biosynthesis inhibitors; (27) inhibitors of
demethylase in sterol biosynthesis; (28) bc.sub.1 complex
fungicides; and salts of compounds of (1) through (28).
[0182] Further descriptions of classes of fungicidal compounds are
provided below.
[0183] Pyrimidinone fungicides (group (4)) include compounds of
Formula A1
##STR00012##
wherein M forms a fused phenyl, thiophene or pyridine ring;
R.sup.11 is C.sub.1-C.sub.6 alkyl; R.sup.12 is C.sub.1-C.sub.6
alkyl or C.sub.1-C.sub.6 alkoxy; R.sup.13 is halogen; and R.sup.14
is hydrogen or halogen.
[0184] Pyrimidinone fungicides are described in PCT Patent
Application Publication WO 94/26722 and U.S. Pat. Nos. 6,066,638,
6,245,770, 6,262,058 and 6,277,858. Of note are pyrimidinone
fungicides selected from the group:
6-bromo-3-propyl-2-propyloxy-4(3H)-quinazolinone,
6,8-diiodo-3-propyl-2-propyloxy-4(3H)-quinazolinone,
6-iodo-3-propyl-2-propyloxy-4(3H)-quinazolinone (proquinazid),
6-chloro-2-propoxy-3-propylthieno[2,3-d]pyrimidin-4(3H)-one,
6-bromo-2-propoxy-3-propylthieno[2,3-d]pyrimidin-4(3H)-one,
7-bromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one,
6-bromo-2-propoxy-3-propylpyrido[2,3-d]pyrimidin-4(3H)-one,
6,7-dibromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one, and
3-(cyclopropylmethyl)-6-iodo-2-(propylthio)pyrido-[2,3-d]pyrimidin-4(3H)--
one.
[0185] Sterol biosynthesis inhibitors (group (27)) control fungi by
inhibiting enzymes in the sterol biosynthesis pathway.
Demethylase-inhibiting fungicides have a common site of action
within the fungal sterol biosynthesis pathway, involving inhibition
of demethylation at position 14 of lanosterol or 24-methylene
dihydrolanosterol, which are precursors to sterols in fungi.
Compounds acting at this site are often referred to as demethylase
inhibitors, DMI fungicides, or DMIs. The demethylase enzyme is
sometimes referred to by other names in the biochemical literature,
including cytochrome P-450 (14DM). The demethylase enzyme is
described in, for example, J. Biol. Chem. 1992, 267, 13175-79 and
references cited therein. DMI fungicides are divided between
several chemical classes: azoles (including triazoles and
imidazoles), pyrimidines, piperazines and pyridines. The triazoles
include azaconazole, bromuconazole, cyproconazole, difenoconazole,
diniconazole (including diniconazole-M), epoxiconazole,
etaconazole, fenbuconazole, fluquinconazole, flusilazole,
flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole,
myclobutanil, penconazole, propiconazole, prothioconazole,
quinconazole, simeconazole, tebuconazole, tetraconazole,
triadimefon, triadimenol, triticonazole and uniconazole. The
imidazoles include clotrimazole, econazole, imazalil, isoconazole,
miconazole, oxpoconazole, prochloraz and triflumizole. The
pyrimidines include fenarimol, nuarimol and triarimol. The
piperazines include triforine. The pyridines include buthiobate and
pyrifenox. Biochemical investigations have shown that all of the
above mentioned fungicides are DMI fungicides as described by K. H.
Kuck et al. in Modern Selective Fungicides--Properties,
Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer
Verlag: New York, 1995, 205-258.
[0186] bc.sub.1 Complex Fungicides (group 28) have a fungicidal
mode of action which inhibits the bc.sub.1 complex in the
mitochondrial respiration chain. The bc.sub.1 complex is sometimes
referred to by other names in the biochemical literature, including
complex III of the electron transfer chain, and
ubihydroquinone:cytochrome c oxidoreductase. This complex is
uniquely identified by Enzyme Commission number EC1.10.2.2. The
bc.sub.1 complex is described in, for example, J. Biol. Chem. 1989,
264, 14543-48; Methods Enzymol. 1986, 126, 253-71; and references
cited therein. Strobilurin fungicides such as azoxystrobin,
dimoxystrobin, enestroburin (SYP-Z071), fluoxastrobin,
kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin,
pyraclostrobin and trifloxystrobin are known to have this mode of
action (H. Sauter et al., Angew. Chem. Int. Ed. 1999, 38,
1328-1349). Other fungicidal compounds that inhibit the bc.sub.1
complex in the mitochondrial respiration chain include famoxadone
and fenamidone.
[0187] Alkylenebis(dithiocarbamate)s (group (1)) include compounds
such as mancozeb, maneb, propineb and zineb. Phenylamides (group
(3)) include compounds such as metalaxyl, benalaxyl, furalaxyl and
oxadixyl. Carboxamides (group (6)) include compounds such as
boscalid, carboxin, fenfuram, flutolanil, furametpyr, mepronil,
oxycarboxin, thifluzamide, penthiopyrad and
N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carbo-
xamide (PCT Patent Publication WO 2003/010149), and are known to
inhibit mitochondrial function by disrupting complex II (succinate
dehydrogenase) in the respiratory electron transport chain. Copper
compounds (group (11)) include compounds such as copper
oxychloride, copper sulfate and copper hydroxide, including
compositions such as Bordeaux mixture (tribasic copper sulfate).
Phthalimides (group (12)) include compounds such as folpet and
captan. Benzimidazole fungicides (group (14)) include benomyl and
carbendazim. Dichlorophenyl dicarboximide fungicides (group (20))
include chlozolinate, dichlozoline, iprodione, isovaledione,
myclozolin, procymidone and vinclozolin.
[0188] Non-DMI sterol biosynthesis inhibitors (group (26)) include
morpholine and piperidine fungicides. The morpholines and
piperidines are sterol biosynthesis inhibitors that have been shown
to inhibit steps in the sterol biosynthesis pathway at a point
later than the inhibitions achieved by the DMI sterol biosynthesis
(group (27)). The morpholines include aldimorph, dodemorph,
fenpropimorph, tridemorph and trimorphamide. The piperidines
include fenpropidin
[0189] Of further note are combinations of compounds of Formula 1
with azoxystrobin, kresoxim-methyl, trifloxystrobin,
pyraclostrobin, picoxystrobin, dimoxystrobin,
metominostrobin/fenominostrobin, carbendazim, chlorothalonil,
quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph,
bromuconazole, cyproconazole, difenoconazole, epoxiconazole,
fenbuconazole, flusilazole, hexaconazole, ipconazole, metconazole,
penconazole, propiconazole, proquinazid, prothioconazole,
tebuconazole, triticonazole, famoxadone, prochloraz, penthiopyrad
and boscalid (nicobifen).
[0190] Preferred for better control of plant diseases caused by
fungal plant pathogens (e.g., lower use rate or broader spectrum of
plant pathogens controlled) or resistance management are mixtures
of a compound of this invention with a fungicide selected from the
group: azoxystrobin, kresoxim-methyl, trifloxystrobin,
pyraclostrobin, picoxystrobin, dimoxystrobin,
metominostrobin/fenominostrobin, quinoxyfen, metrafenone,
cyflufenamid, fenpropidine, fenpropimorph, cyproconazole,
epoxiconazole, flusilazole, metconazole, propiconazole,
proquinazid, prothioconazole, tebuconazole, triticonazole,
famoxadone and penthiopyrad.
[0191] Specifically preferred mixtures (compound numbers refer to
compounds in Index Table A) are selected from the group:
combinations of Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with azoxystrobin, combinations of Compound 1, Compound
2, Compound 3, Compound 4 or Compound 5 with trifloxystrobin,
combinations of Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with pyraclostrobin, combinations of Compound 1,
Compound 2, Compound 3, Compound 4 or Compound 5 with
picoxystrobin, combinations of Compound 1, Compound 2, Compound 3,
Compound 4 or Compound 5 with dimoxystrobin, combinations of
Compound 1, Compound 2, Compound 3, Compound 4 or Compound 5 with
metominostrobin/fenominostrobin, combinations of Compound 1,
Compound 2, Compound 3, Compound 4 or Compound 5 with quinoxyfen,
combinations of Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with metrafenone, combinations of Compound 1, Compound
2, Compound 3, Compound 4 or Compound 5 with cyflufenamid,
combinations of Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with fenpropidine, combinations of Compound 1, Compound
2, Compound 3, Compound 4 or Compound 5 with fenpropimorph,
combinations of C Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with cyproconazole, combinations of Compound 1, Compound
2, Compound 3, Compound 4 or Compound 5 with epoxiconazole,
combinations of Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with flusilazole, combinations of Compound 1, Compound
2, Compound 3, Compound 4 or Compound 5 with metconazole,
combinations of Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with propiconazole, combinations of Compound 1, Compound
2, Compound 3, Compound 4 or Compound 5 with prothioconazole,
combinations of Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with tebuconazole, combinations of Compound 1, Compound
2, Compound 3, Compound 4 or Compound 5 with triticonazole,
combinations of Compound 1, Compound 2, Compound 3, Compound 4 or
Compound 5 with famoxadone, and combinations of C Compound 1,
Compound 2, Compound 3, Compound 4 or Compound 5 with
penthiopyrad.
[0192] The rate of application required for effective control (i.e.
"biologically effective amount") will depend on such factors as the
plant diseases to be controlled, the location, time of year, host
crop, ambient moisture, temperature, and the like. One skilled in
the art can easily determine through simple experimentation the
biologically effective amount necessary for the desired level of
plant disease control.
[0193] The following Tests demonstrate the control efficacy of
compounds of this invention on specific pathogens. The disease
control afforded by the mixtures is not limited, however, to the
pathogenic fungi species exemplified. See Index Table A for
compound descriptions of Formula 1. In Index Table A the
abbreviation Me means methyl. The abbreviation "Ex." stands for
"Example" and is followed by a number indicating in which example
the compound is prepared. In the following table a dash ("-") in
the (R.sup.1).sub.n indicates n is 0 and hydrogen is present at all
available positions.
TABLE-US-00010 INDEX TABLE A ##STR00013## Compound (R.sup.1).sub.n
R.sup.2 R.sup.3 R.sup.4 .sup.1H NMR 1 (Ex. 1) 4-F F 4-F Cl ** 2 --
F 4-F Cl * 3 -- F 4-F H * 4 2-F F 4-F H * 5 4-F F 4-F H * * See
Index Table B for .sup.1H NMR data. ** See synthesis example for
.sup.1H NMR data.
TABLE-US-00011 INDEX TABLE B Compd. No. .sup.1H NMR Data
(CDCl.sub.3 solution unless indicated otherwise).sup.a 2 .delta.
7.25-7.16 (m, 6H), 6.63-6.55 (m, 2H), 6.39 (t, J = 3 Hz, 1H), 6.20
(d, J = 2.4 Hz, 1H), 3.68 (s, 3H), 3.63 (s, 3H), 1.91 (s, 3H). 3
.delta. 7.22-7.17 (m, 5H), 6.60-6.54 (m, 3H), 6.11 (s, 3H), 3.55
(s, 6H), 1.90 (s, 3H). 4 .delta. 7.45-7.40 (m, 1H), 7.35-7.3 (m,
1H), 7.27-7.23 (m, 1H), 7.19-7.15 (m, 1H), 6.72 (s, 1H), 6.58-6.54
(t, J = 8 Hz, 2H), 6.38 (s, 2H), 6.34-6.33 (m, 1H), 3.71 (s, 6H),
1.67 (s, 3H). 5 .delta. 7.18-7.14 (m, 2H), 6.91-6.87 (m, 2H),
6.62-6.56 (m, 2H), 6.49 (s, 1H), 6.14-6.10 (m, 3H), 3.50 (s, 6H)
1.89 (s, 3H). .sup.a1H NMR data are in ppm downfield from
tetramethylsilane. Couplings are designated by (s)-singlet,
(d)-doublet, (t)-triplet, (m)-multiplet.
Biological Examples of the Invention
[0194] General protocol for preparing test suspensions for Tests
A-F: the test compounds were first dissolved in acetone in an
amount equal to 3% of the final volume and then suspended at the
desired concentration (in ppm) in acetone and purified water (50/50
mix by volume) containing 250 ppm of the surfactant Trem.RTM. 014
(polyhydric alcohol esters). The resulting test suspensions were
then used in Tests A-F. Spraying a 200 ppm test suspension to the
point of run-off on the test plants was the equivalent of a rate of
500 g/ha.
Test A
[0195] The test suspension was sprayed to the point of run-off on
wheat seedlings. The following day the seedlings were inoculated
with a spore dust of Erysiphe graminis f. sp. tritici (the causal
agent of wheat powdery mildew) and incubated in a growth chamber at
20.degree. C. for 8 days, after which time disease ratings were
made.
Test B
[0196] The test suspension was sprayed to the point of run-off on
wheat seedlings. The following day the seedlings were inoculated
with a spore suspension of Puccinia recondite f. sp. tritici (the
causal agent of wheat leaf rust) and incubated in a saturated
atmosphere at 20.degree. C. for 24 h, and then moved to a growth
chamber at 20.degree. C. for 7 days, after which time disease
ratings were made.
Test C
[0197] The test suspension was sprayed to the point of run-off on
wheat seedlings. The following day the seedlings were inoculated
with a spore suspension of Septoria tritici (the causal agent of
wheat leaf blotch) and incubated in a saturated atmosphere at
20.degree. C. for 48 h, and then moved to a growth chamber at
20.degree. C. for 19 days, after which time disease ratings were
made.
Test D
[0198] The test suspension was sprayed to the point of run-off on
wheat seedlings. The following day the seedlings were inoculated
with a spore suspension of Septoria nodorum (the causal agent of
wheat glume blotch) and incubated in a saturated atmosphere at
20.degree. C. for 48 h, and then moved to a growth chamber at
20.degree. C. for 7 days, after which time disease ratings were
made.
Test E
[0199] The test suspension was sprayed to the point of run-off on
tomato seedlings. The following day the seedlings were inoculated
with a spore suspension of Alternaria solani (the causal agent of
tomato early blight) and incubated in a saturated atmosphere at
27.degree. C. for 48 h, and then moved to a growth chamber at
20.degree. C. for 5 days, after which time disease ratings were
made.
Test F
[0200] The test suspension was sprayed to the point of run-off on
tomato seedlings. The following day the seedlings were inoculated
with a spore suspension of Botrytis cinerea (the causal agent of
tomato Botrytis) and incubated in a saturated atmosphere at
20.degree. C. for 48 h, and then moved to a growth chamber at
24.degree. C. for 3 days, after which time disease ratings were
made.
[0201] Results for Tests A-F are given in Table A. In the Table, a
rating of 100 indicates 100% disease control and a rating of 0
indicates no disease control (relative to the controls).
TABLE-US-00012 TABLE A Cmpd No. Test A Test B Test C Test D Test E
Test F 1 99 100 97 100 100 98 2 99 100 98 100 99 99 3 99 100 97 100
100 100 4 100 100 98 100 100 99 5 100 100 97 100 100 99
* * * * *